Deficits in learning ability and aging of skin in both strains of senescence-accelerated mouse (SAM) P8 and P10 : neuropathological, neurochemical, histological and pharmacological analysis(Chemical & Pharmacological study)

Animal models of age-related deficiencies are required to elucidate the fundamental mechanisms of age-related deficiencies of learning or aging of skin, the establishment of pertinent animal models that have characteristics very similar to those of human dysfunctions is needed to develop prophylactics/therapeutics against age-related disease. The SAM (senescence-accelerated mouse) has been established as a murine model of SAM strains, groups of related-inbred strains including nine strains of accelerated senescence-prone, short-lived mice (SAMP) and three strains of accelerated senescence-resistant, long-lived mice (SAMR). SAMP strain mice show relatively strain-specific age-associated phenotypic pathologies such as shortened life span and early manifestation of senescence. Among SAMP strain mice, SAMP8 and SAMP10 mice show an age-related deterioration in learning ability and skin aging. We review the neuropathological, neurochemical, histological and pharmacological features of SAM strains, particularly those of SAMP8 and SAMP10 strains, and the effects of several drugs on biochemical, behavioral and histological alterations in the SAMP8

Effect of Epinastine Hydrochloride, a Second-generation Histamine H1-receptor Antagonist, on Sensory Neurons in vitro

Background: Epinastine hydrochloride (epinastine) is a second-generation histamine Hi-receptor antagonist widely used as an anti-allergic and anti-pruritic. To explore possible new aspects of the anti-pruritic mechanism of epinastine, in particular any effects on the peripheral nervous system, we examined epinastine's effects on sensory neurons using cultured murine dorsal root ganglion (DRG). Methods: We performed a quantitative assessment of neurite growth and substance P (SP) release from isolated DRG in the presence versus the absence of epinastine. Mechanism(s) of epinastine’s effects on sensory neurons were detected by examining its neurotoxicity, inhibitory action on nerve growth factor (NGF), and modulatory function on NGFreceptors. Results: The percentage of DRG with outgrowing neurites, total number of neurites, and average extension length of neurites were decreased by epinastine in a concentration-dependent manner. Epinastine did not exhibit any evidence of neurotoxicity on sensory neurons, degradation and inactivation ability on NGF, or effects on expression of NGF receptors. Also, no effects on neural progenitor cells of the central nervous system in culture were observed. Epinastine suppressed capsaicin-induced SP release from DRG neurons in a dosedependent fashion. Conclusions: The results demonstrate that epinastine has inhibitory effects on sensory neuronal growth, which may explain its clinical effects including potent anti-pruritic activity