Disrupting monotony during social isolation stress prevents early development of anxiety and depression like traits in male rats.

BACKGROUND: Although there have been several reports on social isolation induced mood alterations, the independent contribution of monotonous environment in mediating mood alterations has been less studied. In view of the above, the present study is aimed at investigating the relative contribution of monotony towards mood alterations during isolation stress. Monotony was induced in a specially designed isolation chamber in male Sprague-Dawley rats in the presence or absence of isolation by housing animals singly (SH) or in pairs (PH). Novel objects were introduced to disrupt monotony in singly housed animals (SHNO) or paired housed animals (PHNO). Behavioural alterations were assessed using Open field test (OFT), Elevated Plus Maze (EPM) and Forced Swim Test (FST). Neuro-morphological changes in the CA3 region of hippocampus were studied by cresyl violet and golgi-cox staining. Hippocampal serotonin and 5-hydroxy indole acetic acid (5-HIAA) levels were estimated along with the expression of phospho-insulin like growth factor-1 receptor (pIGF-1R) and phospho cyclic AMP response-element binding protein (pCREB). Serotonin was depleted by administering Para-chlorophenylalanine (PCPA) to a separate PH group (PHPCPA), PHNO group (PHNOPCPA) and SHNO group (SHNOPCPA) to determine the role of serotonin in mediating monotony induced emotional mal-adaptations. RESULTS: The results showed anxiety and depression like traits in both PH and SH groups during behavioural test such as OFT, EPM and FST. Pyknosis along with decrease in apical dendritic arborization was observed in the CA3 region of SH group along with decrease in serotonin and reduced expression of pIGF-1R and pCREB. Disrupting monotony through intervention of novel objects in PHNO and SHNO groups ameliorated anxiety and depression like traits and augmented pIGF-1R along with increase in serotonin level. Depletion of hippocampal serotonin level by PCPA administration in PHNOPCPA and SHNOPCPA groups on the other hand resulted in altered mood state despite disruption of monotony by novel objects intervention. CONCLUSION: The findings of our study suggest that monotonous environment independently contributes to impairment in mood state and disrupting monotony by intervention of novel objects during social isolation prevents mood disorders and emotional maladaptation through up regulation of hippocampal pIGF-1R and increase in serotonin.

Chemical composition and antioxidant capacities of phytococktail extracts from trans-Himalayan cold desert.

BACKGROUND: Himalayan plants are widely used in traditional system of medicine both as prophylactics and therapeutics for high altitude maladies. Our aim was to evaluate the antioxidant capacities and bioactive compounds of methanol and n-hexane extracts of the phytococktail comprising of sea buckthorn (Hippophae rhamnoides), apricot (Prunus armeniaca) and roseroot (Rhodiola imbricata) from trans-Himalaya. METHODS: The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and nitric oxide (NO) radical scavenging capacities and lipid peroxidation inhibition (LPI) property of the extracts were determined. Total antioxidant power was determined by ferric reducing/antioxidant power (FRAP) assay. Total polyphenol, flavonoid, flavonol, proanthocyanidin and carotenoid were also estimated for both extracts. We have identified and quantified the phyto-chemotypes present in the methanol and n-hexane extracts by hyphenated gas chromatography/mass spectrometry (GC/MS) technique. RESULTS: Antioxidant capacity assays using DPPH, ABTS, NO, LPI and FRAP exhibited analogous results where the phytococktail showed high antioxidant action. The phytococktail was also found to possess high quantity of total polyphenol, flavonoid, flavonol and carotenoid. A significant and linear correlation was found between the antioxidant capacities and bioactive principles. A total of 32 phyto-chemotypes were identified from these extracts by GC/MS chemometric fingerprinting. Major phyto-chemotypes identified by GC/MS were glycosides, phenylpropanoids and derivatives, terpenoids, alkaloids, phytosterols, fatty acids and esters, alkaloids and derivatives, organic acid esters and aromatic ethers with positive biological and pharmacological actions. CONCLUSION: The phytococktail extracts were found to contain considerable amount of diverse bioactive compounds with high antioxidant capacities. The presence of hydrophilic and lipophilic antioxidants in the phytococktail could have contributed to the higher antioxidant values. Hence, the phytococktail could be used as natural source of antioxidants to ameliorate disorders associated with oxidative stress.

Multi-domain cognitive screening test for neuropsychological assessment for cognitive decline in acclimatized lowlanders staying at high altitude.

BACKGROUND & OBJECTIVES: Ascent to high altitude has been reported to cause hippocampal atrophy and cognitive impairment in mountaineers. We assessed the cognitive performance and probable occurrence of mild cognitive impairment (MCI) in acclimatized lowlanders (ALL) staying at altitudes above 4,300 m for duration above 12 months and validated a multi-domain cognitive screening test (MDCST) for future demographic studies on MCI. METHODS: Following evaluation of sensitivity and correlation of the newly developed MDCST battery with Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scores on a group of 28 individuals, the MDCST battery was validated on a population of 843 ALL staying at high altitude MSL >4,300 m and 862 subjects staying at MSL <230 m. EEG recordings were performed on 840 ALL staying at altitudes above 4,300 m and 743 control subjects staying at MSL <230 m. RESULTS: Percentage prevalence of MCI was 4.18 per cent in the ALL population as assessed by MMSE while that of the LL population was <0.42 per cent. The percentage prevalence of MCI based on calculations from the MDCST scores was 12.4 per cent in the ALL population as compared to 1.19 per cent in the LL population. Decrease in alpha wave amplitude at the T3 and T4 sources in MCI subjects was observed in LL group while there was an increase in amplitude for alpha wave in these regions in the ALL groups. Domain specific MDCST showed decline in immediate recall, procedural memory and mind body co-ordination which was negligible in the LL population. INTERPRETATION & CONCLUSIONS: MDCST exhibited excellent psychometric properties in terms of sensitivity, and test-retest reliability qualifying it to be used as a more effective cognitive measure for assessment of MCI in demographic studies in comparison to traditional measures. Our findings also showed increased prevalence of MCI in ALL population staying for longer durations at high altitude which is neurophysiologically distinct from MCI leading to Alzheimer's disease.

Molecular analysis of knock down resistance (kdr) mutation and distribution of kdr genotypes in a wild population of Culex quinquefasciatus from India.

OBJECTIVE: To investigate the presence of knock down resistance (kdr) mutation, its frequency distribution in the principal vector of bancroftian filariasis, Culex quinquefasciatus from northeastern India, and to relate kdr genotypes with susceptibility and/or resistance to DDT and deltamethrin in this vectors. METHODS: Adult female mosquitoes were collected by aspiration from human dwellings in two villages, Benganajuli and Rikamari, and two military establishments, Field Units I and II. Insecticide susceptibility tests were performed following WHO methods with 4% DDT and 0.05% deltamethrin. Molecular identification of kdr mutation and genotyping of kdr locus was performed by allele-specific PCR (AS-PCR) and direct sequencing in a subset of samples. RESULTS: Mosquitoes were resistant to DDT and showed 11.9-41.2% mortality, whereas the knock down bioassay for deltamethrin suggests complete susceptibility to this insecticide in all study sites except Benganajuli. The result of AS-PCR confirmed the presence of three genotypes: susceptible (SS), resistant (RR) and heterozygous (SR) in the population. Genotype frequencies at kdr locus for DDT-resistant individuals conformed with the Hardy-Weinberg proportion, whereas DDT and deltamethrin susceptible individuals differed significantly (P < 0.05). The efficacy of AS-PCR in detecting the correct genotype was not encouraging. CONCLUSIONS: This is the first report from India on kdr genotyping in C. quinquefasciatus, and it confirms the occurrence of kdr allele in this vector in northeastern India. This finding has serious implications for the filariasis control programmes in India.