Carnosine-like immunoreactivity in the central nervous system of rats during postnatal development

Abstract

In the nervous system of adult rodents, the aminoacylhistidine dipeptides (carnosine and/or homocarnosine) have been shown to be expressed in three main populations of cells: the mature olfactory receptor neurons, a subset of glial cells, and the neuroblasts of the rostral migratory stream. The current study analyzed the distribution of these dipeptides during postnatal development within the rat brain and spinal cord focusing on their pattern of appearance in the glial cells. Double staining methods using antibodies against carnosine and some markers specific for immature (vimentin) and mature (glial fibrillary acidic protein and Rip) glial cell types were used. Glial immunostaining for the aminoacylhistidine dipeptides appears starting from postnatal day 6 and reaches the final distribution in 3-week-old animals. The occurrence of carnosine-like immunoreactivity in astrocytes lags behind that in oligodendrocytes suggesting that, as previously demonstrated by in vitro studies, oligodendrocytes are also able to synthesize carnosine and/or homocarnosine in vivo. Furthermore, the spatiotemporal patterns observed support the hypothesis that the production of these dipeptides coincides with the final stages of glia differentiation. In addition, a strong carnosine-like immunoreactivity is transiently seen in a small population of cells localized in the hypothalamus and in the subfornical organ from birth to postnatal day 21. In these cells, carnosine-like immunoreactivity was not colocalized with any of the glial specific markers used. Moreover, no evidence for colocalization of carnosine and gonadotropin-releasing hormone (GnRH) has been observed.

Structural Basis for Substrate Recognition and Hydrolysis by Mouse Carnosinase CN2

“…L-Carnosine is present at particularly high concentrations in mammalian skeletal muscles and the brain, and it has been implicated in neuroprotection (2), the olfactory system (1), and hypothalamic neuronal networks (3). Our recent observations suggest that central and peripheral administration of L-carnosine at low doses attenuates 2-deoxyglucose-induced hyperglycemia (4) and suppresses peripheral sympathetic nerve activity (5,6).…”

Carnosine: A Possible Drug for Vascular Dementia

“…Although the physiological roles of carnosine in the olfactory bulb are still unclear, olfactory bulb neurons are less sensitive to damage after ischemia compared to hippocampal neurons, despite the accumulation of Zn. Furthermore, carnosine levels have been shown to vary during development [3], and the content of carnosine in muscle is decreased in aged animals [82]. Therefore, carnosine may play protective roles in Zn-induced neuro-degeneration after ischemia in the olfactory bulb.…”

“…In the primary olfactory neurons, carnosine synthase activity is decreased upon denervation and is recovered upon regeneration [20,21]. The sensory neurons may be primarily responsible for the presence of carnosine in the olfactory bulb [3]. Carnosine and its related compounds are not degraded by regular dipeptidases, but are metabolized by specific hydrolytic enzymes, named carnosinases.…”

“…Carnosine and its related compounds, homocarnosine and anserine ( Figure 1A), are found in birds, fish, and mammals, including humans [1][2][3][4]. Carnosine is synthesized by muscle cells, glial cells, and oligodendrocytes [5], and the biggest concentration is observed in skeletal muscle tissue, the stomach, the kidney, cardiac muscle, and the brain [6][7][8].…”

“…During the search for protective substances against Zn-induced neurotoxicity, we found that carnosine exhibits marked inhibitory effects on Zninduced neurotoxicity and proposed its use as a possible therapeutic agent for VD. The level of carnosine varies during development and is low in the aged animals [3]. Therefore, it is highly possible that carnosine protects against external toxins and acts as an endogenous protective substance against neuronal injury and aging.…”