Ageing hippocampus

Traumatic brain injury is the most common cause of death in subjects under the age of 40, and an important risk factor for AD. Loss of hippocampal cells and depletion of ACh and of muscarinic receptors can be attenuated in injured experimental animals, improve blood perfusion in ischemic areas and increase cholinergic transmission in cortex and hippocampus the same mechanism invoked for treatment of VD. 

Veng LM, Mesches MH and Browning MD (2003). Age-related working memory impairment is correlated with increases in the L-type calcium channel protein alD (Cavl.3) in area CA1 of the hippocampus and both are ameliorated by chronic nimodipine treatment. Molecular Brain Research, 110, 193-202. 

Lanahan A et al. Selective alteration of long-term potentiation-induced transcriptional response in hippocampus of aged, memory-impaired rats. J Neurosci 1997 17 2875-2885. 

Decker MW, Pelleymounter MA, Gallagher M. (1988). Effects of training on a spatial memory task on high affinity choline uptake in hippocampus and cortex in young adult and aged rats. J Neurosci. 8(1) 90-9. 

McNay EC, Gold PE. 1999. Extracellular glucose concentrations in the rat hippocampus measured by zero-net-flux effects of microdialysis flow rate, strain, and age. J Neurochem 72(2) 785-790. 

Galliant and Schubert (2007) 13 16 9 NR 15.1 Glu in hippocampus or ACC did not differ between groups. In current smokers, number of cigarettes per day, pack-years, age of smoking initiation did not correlate with Glu. 

McEwen BS (2002) Sex, stress and the hippocampus allostasis, aUostatic load and the aging process. Neurobiol Aging 23(5) 921-939... 

Whether it is possible to raise carnosine levels in human brain is unknown. One study in rats has shown that oral administration of chicken extract (a major source of carnosine in humans too) did provoke an increase in brain carnosine levels a single dose of the chicken extract led to an increase in carnosine levels within 30 min in plasma, but 1 or 2 h duration were required for increased levels of carnosine to be observed in the cerebral cortex, hypthalamus, and hippocampus (Tomonaga et ah, 2007). It is uncertain whether these effects result from direct uptake of the carnosine from plasma or a consequence of de novo synthesis. In a study using senescence-accelerated mice (SAMP8), it was found that oral supplementation with creatine provoked, at 25 weeks of age, a transient 88% increase in muscle carnosine content, accompanied by a 40% increase in anserine content, which coincided with an improvement in resistance to contractile fatigue (Derave et ah, 2008). At 60 weeks, no differences were detectable between the creatine-supplemented and control animals in terms of their muscle... 

Nacher J, Alonso-Llosa G, Rosell DR, McEwen BS (2003) NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol Aging 24 273-284... 

A decline in trophic factors may contribute to aging, and a reduced level of hippocampal 5-HT, receptors in Alzheimer s disease would lead to decreased release of S-100 and increased levels of S-100 within cells (Griffin et al. 1989). The relevance of such changes to neuronal cell loss in the hippocampus and cortex remains to be established. The possibility that other serotonin receptor subtypes may also regulate the release of trophic factors remains to be determined (Whitaker-Azmitia and Azmitia 1991], as does the search for other neuronal growth factors (Zhou and Azmitia 1991]. However, such factors and the involvement of serotonin in their release may subsequently be shown to afford a site of drug action to attenuate cell decline and cognitive impairment. 

Smith MA, Davidson J, Ritchie JG, et al The corticotropin-releasing hormone test in patients with post-traumatic stress order. Biol Psychiatry 26 349-355, 1989 Smith MA, Makino S, Kvetnansky R, et al Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15 1768-1777, 1995 Smith RB, Divoll M, Gillespie WR, et al Effect of subject age and gender on the pharmacokinetics of oral triazolam and temazepam. J Chn Psychopharmacol 3 172-176, 1983... 

Cunha RA, Constantino MC, Sebastiao AM, Ribeiro JA (1995) Modification of Al and A2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat. Neuroreport 6(11) 1583—1588... 

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