A Nine-Year Follow-Up Study of Sleep Patterns and Mortality in Community-Dwelling Older Adults in Taiwan.

A Nine-Year Follow-up Study of Sleep Patterns and Mortality in Community-Dwelling Older Adults in Taiwan.

Sleep. 2013; 36(8): 1187-98
Chen HC, Su TP, Chou P

To simultaneously explore the associations between mortality and insomnia, sleep duration, and the use of hypnotics in older adults.A fixed cohort study.A community in Shih-Pai area, Taipei, Taiwan.A total of 4,064 participants over the age of 65 completed the study.N/A.Insomnia was classified using an exclusionary hierarchical algorithm, which categorized insomnia as “no insomnia,” “subjective poor sleep quality,” “Pittsburgh Sleep Quality Index > 5 insomnia,” “1-month insomnia disorder,” and “6-month insomnia disorder.” The main outcome variables were 9-year all-cause mortality rates. In the all-cause mortality analyses, when hypnotic use, depressive symptoms and total sleep time were excluded from a proportional hazards regression model, subjects with “Pittsburgh Sleep Quality Index > 5 insomnia” had a higher mortality risk (HR: 1.21, 95% CI: 1.01-1.45). In the full model, frequent hypnotic use and long sleep duration predicted higher mortality rates. However, the increased mortality risk for subjects with “Pittsburgh Sleep Quality Index > 5 insomnia” was not observed in the full model. On the contrary, individuals with a 6-month DSM-IV insomnia disorder had a lower risk for premature death (HR: 0.64, 95% CI: 0.43-0.96).Long sleep duration and frequent hypnotics use predicted an increased mortality risk within a community-dwelling sample of older adults. The association between insomnia and mortality was affected by insomnia definition and other parameters related to sleep patterns.Chen HC; Su TP; Chou P. A nine-year follow-up study of sleep patterns and mortality in community-dwelling older adults in Taiwan. SLEEP 2013;36(8):1187-1198. HubMed – depression

Continuous modulation of action potential firing by a unitary GABAergic connection in the globus pallidus in vitro.

J Neurosci. 2013 Jul 31; 33(31): 12805-9
Bugaysen J, Bar-Gad I, Korngreen A

The firing patterns of neurons in the globus pallidus (GP) are affected by two major sources of GABAergic inhibition: striatal afferents and local axon collaterals. Local GABAergic GP-GP synapses display short-term depression (STD) and very sparse connectivity. At the high presynaptic firing rates typical in the GP, one would expect this STD to be complete, practically canceling the postsynaptic impact of the synapse. To investigate the apparent paradox of a synapse not affecting its postsynaptic neuron, we performed dual whole-cell recordings in acute brain slices from rats and recorded, for the first time, unitary IPSPs from a GP-GP GABAergic connection. We show that at high presynaptic firing rates the unitary connection continuously modulates the postsynaptic firing rate through a combination of large chloride driving force, unitary IPSP summation, and incomplete synaptic depression. Our findings indicate that, despite substantial STD and sparse connectivity, local GABAergic axon collaterals in the GP may echo the changes in presynaptic firing frequency across postsynaptic targets. HubMed – depression

Knockdown of prodynorphin gene prevents cognitive decline, reduces anxiety, and rescues loss of group 1 metabotropic glutamate receptor function in aging.

J Neurosci. 2013 Jul 31; 33(31): 12792-804
Ménard C, Tse YC, Cavanagh C, Chabot JG, Herzog H, Schwarzer C, Wong TP, Quirion R

Expression of dynorphin, an endogenous opioid peptide, increases with age and has been associated with memory impairments in rats. In human, prodynorphin (Pdyn) gene polymorphisms might be linked to cognitive function in the elderly. Moreover, elevated dynorphin levels have been reported in postmortem samples from Alzheimer’s disease patients. However, the cellular and molecular processes affected by higher dynorphin levels during aging remain unknown. Using Pdyn(-/-) mice, we observed significant changes in the function and expression of Group 1 metabotropic glutamate receptor (mGluR). Compared with age-matched wild-type (WT) littermates, we found increased expression of mGluR1? and mGluR5 in the hippocampus and cortex of old, but not young, Pdyn(-/-) mice. Increased Group 1 mGluR expression in aged Pdyn(-/-) mice was associated with enhanced mGluR-mediated long-term depression, a form of synaptic plasticity. Notably, whereas aged WT mice developed spatial and recognition memory deficits, aged Pdyn(-/-) mice performed similarly as young mice. Pharmacological treatments with 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide, a positive modulator of mGlu5 receptors, or norbinaltorphimine, an antagonist for dynorphin-targeted ?-opioid receptor, rescued memory in old WT mice. Conversely, mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride impaired spatial memory of old Pdyn(-/-) mice. Intact cognition in aged Pdyn(-/-) mice paralleled with increased expression of Group 1 mGluR-related genes Homer 1a and Arc. Finally, aged Pdyn(-/-) mice displayed less anxiety-related behaviors than age-matched WT mice. Together, our results suggest that elevated Pdyn expression during normal aging reduces mGluR expression and signaling, which in turn impairs cognitive functions and increases anxiety. HubMed – depression

Integrity of mGluR-LTD in the Associative/Commissural Inputs to CA3 Correlates with Successful Aging in Rats.

J Neurosci. 2013 Jul 31; 33(31): 12670-8
Yang S, Megill A, Ardiles AO, Ransom S, Tran T, Koh MT, Lee HK, Gallagher M, Kirkwood A

The impact of aging on cognitive capabilities varies among individuals ranging from significant impairment to preservation of function on par with younger adults. Research on the neural basis for age-related memory decline has focused primarily on the CA1 region of the hippocampus. However, recent studies in elderly human and rodents indicate that individual differences in cognitive aging are more strongly tied to functional alterations in CA3 circuits. To examine synaptic plasticity in the CA3 region, we used aged rats behaviorally characterized in a hippocampal-dependent task to evaluate the status of long-term potentiation and long-term depression (LTP and LTD) in the associative/commissural pathway (A/C?CA3), which provides the majority of excitatory input to CA3 pyramidal neurons. We found that, unlike in CA1 synapses, in A/C?CA3 LTP is minimally affected by age. However, two forms of LTD, involving NMDA and metabotropic glutamate receptors (mGluR), are both greatly reduced in age-impaired rats. Age-unimpaired rats, in contrast, had intact mGluR LTD. These findings indicate that the integrity of mGluR-LTD at A/C?CA3 inputs may play a crucial role in maintaining the performance of CA3 circuitry in aging. HubMed – depression