Aging induced memory impairment

Plant-originated anti-ChEs, such as huperzine A, have been used for thousands of years in the treatment of aging-induced memory impairment (Haviv et al., 2007). In 1877, prior to the discovery of ACh as a neurotransmitter in the brain, physostigmine (eserine)— a carbamate extracted from the seeds of Physostigma venenosum—became the first cholinesterase inhibitor used therapeutically to control increased ocular pressure caused by wide-angle glaucoma (Taylor, 1996). 

To reveal the cognition-enhancing potential of the S-HTj antagonists, studies in age-related memory impairment have been carried out with psy-chiatrically healthy subjects impaired with scopolamine and patients with dementia. In a randomized double-blind, double-dummy, four-way crossover study in a small number of subjects, each psychiatrically healthy male subject received placebo, scopolamine [0.4 mg im], scopolamine plus alosetron [10 J,g iv], or alosetron [250 Jg] [Preston 1994 Preston et al. 1991). Assessments of verbal and spatial memory, sedation, and sustained attention were performed before and after treatment. The main results from the study were that scopolamine induced robust deficits on all primary variables measured, the reduction in verbal and spatial memories being attenuated by 10- Jg and 250- Jg doses of alosetron, respectively. No effects on the sedation or on changes in attention were noted. 

Ginkgo 1 2 151 million (36), 395.68 million (7) Age-related macular degeneration treatment, age-related memory impairment, altitude Antidepressant-induced sexual dysfunction, seasonal affective disorder, tinnitus... 

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. 

Citicoline (cytidinediphosphate-choline/CDP-choline 26) is an intermediate in the biosynthesis of acetylcholine. It has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, and AD. Studies in mice have indicated a protective effect of citicohne against memory impairment induced by adverse environments. A human study recruited 30 patients with mild to moderate AD in a double-blind, randomized and placebo-controlled clinical trial... 

Takahashi et al 2003). Expression of active PAK in hippocampal neurons could prevent the effects induced by A6 oligomers, and significantly, pharmacological PAK inhibition in adult mice was sufficient to cause drebrin loss and memory impairment (Zhao et al., 2006). Thus, these findings indicate that loss of PAK3 and/or PAKl is involved in both developmental-dependent and age-dependent cognitive deficits, such as observed in AD. 

The xanthine derivative, propentofyllin, up-regulates NGF synthesis 10-fold in cultured astrocytes (Shinoda et al., 1990). This was of particular interest, as the drug reverses learning and memory impairment in aged rats (Goto et al., 1987) and protects against delayed, ischaemically induced neuronal death in the hippocampus. Shinoda and co-workers (Shinoda et al., 1990) therefore speculated that the beneficial effects of propentofyllin, in part, could be due to an induction of NGF synthesis in astrocytes. 

Kami-untan-to (KUT) > Kampo traditional preparation for treating age-related memory loss and dementia. oral administration increased choline acetyltransferase activity in frontoparietal cortex and reduced cognitive impairment in forebrain-lesioned rats. KUT indirectly increases available achetylcholine by inducing increased transcription of choline acetyltransferase (ChAT) and Nerve Growth Factor (NGF) mRNA. putative mechanism is stimulated NGF production resulting in increased ChAT production, and indirectly, increased Acetylcholine production (ACh). 

Block Rl, De Voe M, Stanley M, etal. Memory performance in individuals with primary degenerative dementia its similarity to diazepam-induced impairments. Exp Aging Res 1985 11 151-155. 

S100B Overexpression Female specific hyperactivity, lack of habituation to novelty, reduced T-maze spontaneous alternation rate, abnormal exploratory behavior Enhanced astrocytosis and neurite proliferation Impaired learning and memory, increased dendrite density, enhanced age-related loss of dendrites Inhibitory effect on cardiac hypertrophy Increased susceptibility to hypoxia-ischemia Increased apoptosis after myocardial infarction Enhanced neuroinflammation and neuronal dysfunction induced by amyloid-(3... 

Of course, one caveat for all the aforementioned studies is that they were performed in nonimpaired animals. However, R065-7199 improves scopolamine-induced deficits in this task (37) and recent data from Foley et al. (102) showed that chronic treatment with SB-271046 (once daily, 40 d) improved the age-related impairment in spatial learning and memory in 20-mo-old Wistar rats, an effect also seen in aged Fisher 344 rats (103). Further testing of 5-htg receptor antagonists in glutamate-deficiency models and neurodevelopment-deficiency models is suggested. 

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