The neuroanatomical model of post-stroke depression: towards a change of focus?

One third of all stroke survivors develop post-stroke depression (PSD). Depressive symptoms adversely affect rehabilitation and significantly increase risk of death in the post-stroke period. One of the theoretical views on the determinants of PSD focuses on psychosocial factors like disability and social support. Others emphasize biologic mechanisms such as disruption of biogenic amine neurotransmission and release of proinflammatory cytokines. The "lesion location" perspective attempts to establish a relationship between localization of stroke and occurrence of depression, but empirical results remain contradictory. These divergences are partly related to the fact that neuroimaging methods, unlike neuropathology, are not able to assess precisely the full extent of stroke-affected areas and do not specify the different types of vascular lesions. We provide here an overview of the known phenomenological profile and current pathogenic hypotheses of PSD and present neuropathological data challenging the classic "single-stroke"-based neuroanatomical model of PSD. We suggest that vascular burden due to the chronic accumulation of small macrovascular and microvascular lesions may be a crucial determinant of the development and evolution of PSD.

Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice.

Patients with the early-onset Alzheimer's disease P117L mutation in the presenilin-1 gene (PS-1) present pathological hallmarks in the hippocampus, the frontal cortex and the basal ganglia. In the present work we determined by immunohistochemistry which brain regions were injured in the transgenic PS-1 P117L mice, in comparison to their littermates, the B6D2 mice. Furthermore, as these regions are involved in novelty detection, we investigated the behavior of these mice in tests for object and place novelty recognition. Limited numbers of senile plaques and neurofibrillary tangles were detected in aged PS-1 P117L mice in the CA1 only, indicating that the disease is restrained to an initial neuropathological stage. Western blots showed a change in PSD-95 expression (p=0.03), not in NR2A subunit, NR2B subunit and synaptophysin expressions in the frontal cortex, suggesting specific synaptic alterations. The behavioral tests repeatedly revealed, despite a non-significant preference for object or place novelty, maladaptive exploratory behavior of the PS-1 P117L mice in novel environmental conditions, not due to locomotor problems. These mice, unlike the B6D2 mice, were less inhibited to visit the center of the cages (p=0.01) and they continued to move excessively in the presence of a displaced object (p=0.021). Overall, the PS-1 P117L mice appear to be in an initial Alzheimer's disease-like neuropathological stage, and they showed a lack of reaction toward novel environmental conditions.

Differential impact of lacunes and microvascular lesions on poststroke depression.

BACKGROUND AND PURPOSE: Previous studies have postulated that poststroke depression (PSD) might be related to cumulative vascular brain pathology rather than to the location and severity of a single macroinfarct. We performed a detailed analysis of all types of microvascular lesions and lacunes in 41 prospectively documented and consecutively autopsied stroke cases. METHODS: Only cases with first-onset depression <2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models. RESULTS: Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher lacune scores in basal ganglia, thalamus, and deep white matter were associated with an increased PSD risk. In contrast, microinfarct and diffuse or periventricular demyelination scores were not increased in PSD. The combined lacune score (thalamic plus basal ganglia plus deep white matter) explained 25% of the variability of PSD occurrence. CONCLUSIONS: The cumulative vascular burden resulting from chronic accumulation of lacunar infarcts within the thalamus, basal ganglia, and deep white matter may be more important than single infarcts in the prediction of PSD.

Maladie d'Alzheimer : Etude des marqueurs pathologiques dans le cortex frontal humain et corrélations anatomo-cliniques

La maladie d'Alzheimer (MA), forme de démence la plus fréquente, est caractérisée précocement par des troubles de la mémoire, puis par une détérioration cognitive progressive, corrélée avec la progression des lésions cérébrales que sont les dépôts de protéine ß-amyloïde, notamment dans les plaques séniles, et la dégénérescence neurofibrillaire qui touche en priorité les grands neurones pyramidaux de l'hippocampe et du cortex cérébral. La perte ou les dommages synaptiques sont aussi prépondérants et conduisent à la mort neuronale et à la perte de réseaux fonctionnels notamment au niveau des protéines présynaptiques comme la synaptophysine et postsynaptiques comme PSD-95 (Leuba et al. 2008), ainsi que des récepteurs NMDA (NMDAR) liés à PSD-95 et jouant un rôle prédominant dans le fonctionnement synaptique. Notre étude s'est portée une des régions du cortex frontal correspondant à l'aire de Brodmann 10, encore peu étudiée dans la littérature scientifique, qui peut être touchée de manière plus ou moins importante dans la MA, entraînant des troubles de l'humeur et du comportement ainsi que des répercussions sur les fonctions exécutives. L'étude a pour but d'identifier et de quantifier les dépôts de protéine ß-amyloïde et les lésions neurofibrillaires ainsi que les changements de protéines synaptiques et de récepteurs NMDA dans cette région entre une population contrôle et AD, et de la comparer avec d'autres régions déjà partiellement étudiées dans le laboratoire, notamment l'aire 9 qui lui est adjacente et les aires cingulaires 24 et 25. L'analyse est faite de manière qualitative et semi-quantitative au microscope optique sur des coupes colorées avec des méthodes immunohistochimiques. De possibles corrélations anatomo-cliniques sont recherchées dans les cas AD. La région FC10 est touchée par la MA avec une présence de plaques séniles et de dégénérescences neurofibrillaires plus marquées chez les cas atteints de la MA ce qui n'est pas le cas des protéines synaptiques. Le comportement des deux marqueurs pathologiques dans FC10 est comparable aux autres régions cérébrales étudiées notamment à la région adjacente, FC9, contrairement aux marqueurs synaptiques qui selon la région ont un comportement plus variable. L'effet de l'âge dans l'évolution de la physiopathologie de la MA pour les marqueurs pathologiques a été mis en évidence dans la région FC10. Les régions EC et FC9 n'ont pas montré de microhémorragie synonyme d'une possible contribution vasculaire. L'étude de cette région a permis de mettre en évidence l'implication de FC10 dans la MA. Elle montre des points communs avec les autres régions cérébrales notamment vis-à-vis des plaques séniles et des DNF.

Specific targeting of pro-death NMDA receptor signals with differing reliance on the NR2B PDZ ligand.

NMDA receptors (NMDARs) mediate ischemic brain damage, for which interactions between the C termini of NR2 subunits and PDZ domain proteins within the NMDAR signaling complex (NSC) are emerging therapeutic targets. However, expression of NMDARs in a non-neuronal context, lacking many NSC components, can still induce cell death. Moreover, it is unclear whether targeting the NSC will impair NMDAR-dependent prosurvival and plasticity signaling. We show that the NMDAR can promote death signaling independently of the NR2 PDZ ligand, when expressed in non-neuronal cells lacking PSD-95 and neuronal nitric oxide synthase (nNOS), key PDZ proteins that mediate neuronal NMDAR excitotoxicity. However, in a non-neuronal context, the NMDAR promotes cell death solely via c-Jun N-terminal protein kinase (JNK), whereas NMDAR-dependent cortical neuronal death is promoted by both JNK and p38. NMDAR-dependent pro-death signaling via p38 relies on neuronal context, although death signaling by JNK, triggered by mitochondrial reactive oxygen species production, does not. NMDAR-dependent p38 activation in neurons is triggered by submembranous Ca(2+), and is disrupted by NOS inhibitors and also a peptide mimicking the NR2B PDZ ligand (TAT-NR2B9c). TAT-NR2B9c reduced excitotoxic neuronal death and p38-mediated ischemic damage, without impairing an NMDAR-dependent plasticity model or prosurvival signaling to CREB or Akt. TAT-NR2B9c did not inhibit JNK activation, and synergized with JNK inhibitors to ameliorate severe excitotoxic neuronal loss in vitro and ischemic cortical damage in vivo. Thus, NMDAR-activated signals comprise pro-death pathways with differing requirements for PDZ protein interactions. These signals are amenable to selective inhibition, while sparing synaptic plasticity and prosurvival signaling.

Alzheimer's disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression.

BACKGROUND: Alzheimer's disease (AD) is the most frequent form of dementia in the elderly and no effective treatment is currently available. The mechanisms triggering AD onset and progression are still imperfectly dissected. We aimed at deciphering the modifications occurring in vivo during the very early stages of AD, before the development of amyloid deposits, neurofibrillary tangles, neuronal death and inflammation. Most current AD models based on Amyloid Precursor Protein (APP) overproduction beginning from in utero, to rapidly reproduce the histological and behavioral features of the disease within a few months, are not appropriate to study the early steps of AD development. As a means to mimic in vivo amyloid APP processing closer to the human situation in AD, we used an adeno-associated virus (AAV)-based transfer of human mutant APP and Presenilin 1 (PS1) genes to the hippocampi of two-month-old C57Bl/6 J mice to express human APP, without significant overexpression and to specifically induce its amyloid processing. RESULTS: The human APP, βCTF and Aβ42/40 ratio were similar to those in hippocampal tissues from AD patients. Three months after injection the murine Tau protein was hyperphosphorylated and rapid synaptic failure occurred characterized by decreased levels of both PSD-95 and metabolites related to neuromodulation, on proton magnetic resonance spectroscopy ((1)H-MRS). Astrocytic GLT-1 transporter levels were lower and the tonic glutamatergic current was stronger on electrophysiological recordings of CA1 hippocampal region, revealing the overstimulation of extrasynaptic N-methyl D-aspartate receptor (NMDAR) which precedes the loss of long-term potentiation (LTP). These modifications were associated with early behavioral impairments in the Open-field, Y-maze and Morris Mater Maze tasks. CONCLUSIONS: Altogether, this demonstrates that an AD-like APP processing, yielding to levels of APP, βCTF and Aβ42/Aβ40 ratio similar to those observed in AD patients, are sufficient to rapidly trigger early steps of the amyloidogenic and Tau pathways in vivo. With this strategy, we identified a sequence of early events likely to account for disease onset and described a model that may facilitate efforts to decipher the factors triggering AD and to evaluate early neuroprotective strategies.

Effects of neurotrophins on synaptic protein expression in the visual cortex of dark reared rats.

Total lack of visual experience [dark rearing (DR)] is known to prolong the critical period and delay development of sensory functions in mammalian visual cortex. Recent results show that neurotrophins (NTs) counteract the effects of DR on functional properties of visual cortical cells and exert a strong control on critical period duration. NTs are known to modulate the development and synaptic efficacy of neurotransmitter systems that are affected by DR. However, it is still unknown whether the actions of NTs in dark-reared animals involve interaction with neurotransmitter systems. We have studied the effects of DR on the expression of key molecules in the glutamatergic and GABAergic systems in control and NT-treated animals. We have found that DR reduced the expression of the NMDA receptor 2A subunit and its associated protein PSD-95 (postsynaptic density-95), of GRIP (AMPA glutamate receptor interacting protein), and of the biosynthetic enzyme GAD (glutamic acid decarboxylase). Returning dark-reared animals to light for 2 hr restored normal expression of the above-mentioned proteins almost completely. NT treatment specifically counteracts DR effects; NGF acts primarily on the NMDA system, whereas BDNF acts primarily on the GABAergic system. Finally, the action of NT4 seems to involve both excitatory and inhibitory systems. These data demonstrate that different NTs counteract DR effects by modulating the expression of key molecules of the excitatory and inhibitory neurotransmitter systems

Reactive dissolution of sedimentary rocks in flue gas desulfurization : modeling and experimental investigation

Svavel förekommer i kol och olja och oxideras vid förbränning till svaveldioxid (SO2). Årligen utsläpps stora mängder svaveldioxid som åstadkommer sura regn, minskning av stratosfäriskt ozon och sjukdomar. Av dessa orsaker är det nödvändigt att minska utsläppen av svaveldioxid. Den teknologi som rör planering av reaktorer och processer för rökgasavsvavling (FGD) har utvecklats kraftigt och idag använder man olika typer av lösningar. De vanligaste alternativen för FGD är våtskrubber- och semitorra skrubbersystem (Spray Dry Scrubbers, SDS) och injektionsprocesser för absorbenter. SDS-processer har studerats bland annat av Ahlbeck [4] och Klingspor [5] och injektionsprocesser av Alvfors [6]. Kalksten, som i huvusak består av kalciumkarbonat, används i rökgasavsvavling på grund av sin förmåga att binda svavel i form av sulfatsalter. Den vanligaste rökgasavsvavlingsmetoden är våtskrubbning, där det sedimentära stenmaterialets upplösningshastighet är en av de faktorer som påverkar resultatet mest. Utvärdering av kalkstensreaktivitet är därför speciellt viktig vid planering och drift av anläggningar för rökgasavsvavling. Målsättningen med detta arbete var att modellera upplösningen av olika typers kalksten för att få en kvantitativ utvärdering av kvaliteten på de analyserade proverna. Därtill testades även karbonatbiprodukter från stålindustrin för att utvärdera möjligheter att använda andra råmaterial. Det transienta förloppet har analyserats, varvid upplösningshastigheten modellerades bl.a. i avseende på tid och pH. Under arbetets gång har antalet empiriska korrelationer minskats till fördel för fysikaliska modeller av diffusiva och konvektiva masstransportfenomen. En målsättning var att skapa en effektiv och snabb metod för att testa olika absorbenter för rökgasavsvavling under transienta förlopp. I arbetet användes PSD-analys, gjordes pH-mätningar och andra utvärderingar av de fysikaliska parametrar som ingår i beräkningarna. On-line mätningar för de icke-stationära variablerna tid och pH ger möjlighet att eliminera osäkerheter. Vissa modeller kan vara komplicerade. En modell för upplösningshastigheten med mer detaljerad utvärdering av parametrar och färre approximationer är därför nödvändig då man vill utvärdera reaktionshastigheten för fasta partiklar i sur miljö. Arbetet utfördes under fyra år och fem peer review-artiklar ingår i avhandlingen.

Different stress modalities result in distinct steroid hormone responses by male rats

Since both paradoxical sleep deprivation (PSD) and stress alter male reproductive function, the purpose of the present study was to examine the influence of PSD and other stressors (restraint, electrical footshock, cold and forced swimming, N = 10 per group) on steroid hormones in adult Wistar male rats. Rats were submitted to chronic stress for four days. The stressors (footshock, cold and forced swimming) were applied twice a day, for periods of 1 h at 9:00 and 16:00 h. Restrained animals were maintained in plastic cylinders for 22 h/day whereas PSD was continuous. Hormone determination was measured by chemiluminescent enzyme immunoassay (testosterone), competitive immunoassay (progesterone) and by radioimmunoassay (corticosterone, estradiol, estrone). The findings indicate that PSD (13.7 ng/dl), footshock (31.7 ng/dl) and cold (35.2 ng/dl) led to lower testosterone levels compared to the swimming (370.4 ng/dl) and control (371.4 ng/dl) groups. However, progesterone levels were elevated in the footshock (4.5 ng/ml) and PSD (5.4 ng/ml) groups compared to control (1.6 ng/ml), swimming (1.1 ng/ml), cold (2.3 ng/ml), and restrained (1.2 ng/ml) animals. Estrone and estradiol levels were reduced in the PSD, footshock and restraint groups compared to the control, swimming and cold groups. A significant increase in corticosterone levels was found only in the PSD (299.8 ng/ml) and footshock (169.6 ng/ml) groups. These changes may be thought to be the full steroidal response to stress of significant intensity. Thus, the data suggest that different stress modalities result in distinct steroid hormone responses, with PSD and footshock being the most similar.

Effect of sildenafil (Viagra®) on the genital reflexes of paradoxical sleep-deprived male rats

Since there is evidence that paradoxical sleep deprivation (PSD) elicits penile erection (PE) and ejaculation (EJ), and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group). The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 ± 22 ng/dL) than in controls (365 ± 38 ng/dL), whereas progesterone (0.9 ± 0.1 vs 5.4 ± 1 ng/mL) and plasma dopamine (103.4 ± 30 vs 262.6 ± 77 pg/mL) increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone) and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Anandamide injected into the lateral ventricle of the brain inhibits submandibular salivary secretion by attenuating parasympathetic neurotransmission

Our objective was to determine the effect of arachidonylethanolamide (anandamide, AEA) injected intracerebroventricularly (icv) into the lateral ventricle of the rat brain on submandibular gland (SMG) salivary secretion. Parasympathetic decentralization (PSD) produced by cutting the chorda tympani nerve strongly inhibited methacholine (MC)-induced salivary secretion while sympathetic denervation (SD) produced by removing the superior cervical ganglia reduced it slightly. Also, AEA (50 ng/5 µL, icv) significantly decreased MC-induced salivary secretion in intact rats (MC 1 µg/kg: control (C), 5.3 ± 0.6 vs AEA, 2.7 ± 0.6 mg; MC 3 µg/kg: C, 17.6 ± 1.0 vs AEA, 8.7 ± 0.9 mg; MC 10 µg/kg: C, 37.4 ± 1.2 vs AEA, 22.9 ± 2.6 mg). However, AEA did not alter the significantly reduced salivary secretion in rats with PSD, but decreased the slightly reduced salivary secretion in rats with SD (MC 1 µg/kg: C, 3.8 ± 0.8 vs AEA, 1.4 ± 0.6 mg; MC 3 µg/kg: C, 14.7 ± 2.4 vs AEA, 6.9 ± 1.2 mg; P < 0.05; MC 10 µg/kg: C, 39.5 ± 1.0 vs AEA, 22.3 ± 0.5 mg; P < 0.001). We showed that the inhibitory effect of AEA is mediated by cannabinoid type 1 CB1 receptors and involves GABAergic neurotransmission, since it was blocked by previous injection of the CB1 receptor antagonist AM251 (500 ng/5 µL, icv) or of the GABA A receptor antagonist, bicuculline (25 ng/5 µL, icv). Our results suggest that parasympathetic neurotransmission from the central nervous system to the SMG can be inhibited by endocannabinoid and GABAergic systems.

Carponate precipitation with carbon dioxide gas

The aim of this thesis research work focused on the carbonate precipitation of magnesium using magnesium hydroxide Mg(OH)2 and carbon dioxide (CO2) gas at ambient temperature and pressure. The rate of dissolution of Mg(OH)2 and precipitation kinetics were investigated under different operating conditions. The conductivity and pH of the solution were inline monitored by a Consort meter and the solid samples gotten from the precipitation reaction were analysed by a laser diffraction analyzer Malvern Mastersizer to obtain particle size distributions (PSD) of crystal samples. Also the Mg2+ concentration profiles were determined from the liquid phase of the precipitate by ion chromatography (IC) analysis. Crystal morphology of the obtained precipitates were also investigated and discussed in this work. For the carbonation reaction of magnesium hydroxide in the present work, it was found that magnesium carbonate trihydrate (nesquehonite) was the main product and its formation occurred at a pH of around 7-8. The stirrer speed has a significant effect on the dissolution rate of Mg(OH)2. The highest obtained Mg2+ concentration level was 0.424 mol L-l for the 470 rpm and 0.387 mol L-1 for the 560 rpm which corresponded to the processing time of 45 mins and 40 mins respectively. The particle size distribution shows that the average particle size keeps increasing during the reaction as the CO2 is been fed to the system. The carbonation process is kinetically favored and simple as nesquehonite formation occurs in a very short time. It is a thermodynamically and chemically stable solid product, which allows for a long-term storage of CO2. Since the carbonation reaction is a complex system which includes dissolution of magnesium hydroxide particles, absorption of CO2, chemical reaction and crystallization, the dissolution of magnesium hydroxide was studied in hydrochloric acid (HCl) solvent with and without nitrogen (N2) inert gas. It was found on the dissolution part that the impeller speed had effect on the dissolution rate. The higher the impeller speed the higher the pH of the solution, although for the highest speed of 650rpm it was not the case. Therefore, it was concluded that the optimum speed of the stirrer was 560rpm. The influence of inert gas N2 on the dissolution rate of Mg(OH)2 particles could be seen based on measured pH, electric conductivity and Mg2+ concentration curves.

Jauhatusparametrien vaikutus jauhatustuotteen partikkelikokoon ja suodattuvuuteen

Tämän diplomityön tarkoituksena on tutkia ensin jauhatusparametrien vaikutus rikastushiekan hienousasteeseen eli miten partikkelikokojakaumaa kuvaavat partikkelikoot muuttuvat. Tämän jälkeen tutkitaan miten rikastushiekan hienousasteen muuttuminen vaikuttaa jauhettujen rikastushiekkalietenäytteiden suodattuvuuteen. Partikkelikokojakauman variaatioista yritetään löytää yhteys suodinkakun ominaisvastuksen ja huokoisuuden välillä. Jauhatus suoritettiin laboratoriomittakaavan helmimyllyllä märkäjauhatuksena. Jauhatusta varten tehtiin kolmitasoinen faktorikoesuunnitelma, jossa muuttujina ovat lasihelmien halkaisija, jauhatusaika ja sekoitinelimen pyörimisnopeus. Suodatus toteutettiin vakiopainesuodatuksena kolmella eri suodatuspaineella Nutsche-suodattimella. Työn tuloksista saatiin selville, että partikkelikokojakauman leveys korreloi suodinkakun ominaisvastuksen kanssa. Kun partikkelikokojakauma leveys muuttui kapeammaksi, saatiin kakun ominaisvastus pienemmäksi ja suodatukseen kulunut aika lyheni. Kapein partikkelikokojakauman leveys saatiin suurimmalla helmen halkaisijalla, pisimmällä jauhatusajalla sekä suurimmalla sekoitusnopeudella.

Characterization of Wastes from Natural Rubber and Rubber Wood Processing Industries and Their Utilization for Biomethanation

The research work which was carried out to characterization of wastes from natural rubber and rubber wood processing industries and their utilization for biomethanation. Environmental contamination is an inevitable consequence of human activity. The liquid and solid wastes from natural rubber based industries were: characterized and their use for the production of biogas investigated with a view to conserve conventional energy, and to mitigate environmental degradation.Rubber tree (flevea brasiliensis Muell. Arg.), is the most important commercial source of natural rubber and in india. Recently, pollution from the rubber processing factories has become very serious due to the introduction of modern methods and centralized group processing practices.The possibility of the use of spent slurry as organic manure is discussed.l0 percent level of PSD, the activity of cellulolytic, acid producing,proteolytic, lipolytic and methanogenic bacteria were more in the middle stage of methanogenesis.the liquid wastes from rubber processing used as diluents in combination with PSD, SPE promoted more biogas production with high methane content in the gas.The factors that favour methane production like TS, VS, cellulose and hemicellulose degradation were favoured in this treatment which led to higher methane biogenesis.The results further highlight ways and means to use agricultural wastes as alternative sources of energy.