Culture of dorsal root ganglion neurons from aged rats: Effects of acetyl‐l‐carnitine and NGF

Abstract

In vitro neuronal preparations are used to study the action mechanism of substances which are active in normal and pathological brain aging. One major concern with in vitro assays is that the use of embryonic or adult neurons may hamper an appreciation of the relevance of these substances on aged nervous tissue. In the present study for the first time cultures of aged dorsal root ganglia from 24-months-old rats were maintained in vitro up to 2 weeks. This model was used to investigate the neurotrophic/neuroprotective action of nerve growth factor and acetyl-L-carnitine. A large population of aged dorsal root ganglia neurons was responsive to nerve growth factor (100 ng/ml). Nerve growth factor induced an increase of initial rate of axonal regeneration and influenced the survival time of these neurons. Acetyl-L-carnitine (250 microM) did not affect the axonal regeneration but substantially attenuated the rate of neuronal mortality. A significant difference was evident between the acetyl-L-carnitine-treated and the untreated neurons from the first cell counting (day 3 in culture). After 2 weeks the number of aged neurons treated with acetyl-L-carnitine was almost double that of the controls. The effects of acetyl-L-carnitine on aged DRG neurons potentially explain the positive effects in clinical and in vivo experimental studies.

Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis. A possible mechanism for Alzheimer's disease.

“…It was shown that in mature oligodendrocytes (10) NTR and p140 trkA are expressed on the cell surface, NGF receptor binding affinity is in the picomolar range (35), and NGF signals through p140 trkA leading to cell survival (36). Indeed, in the adult organism, presumptively through coordinated binding to both p75 NTR and p140 trkA , NGF can augment survival of aged neurons (37)(38)(39) as well as the survival of neurons after various injuries like hypoglycemia (40,41), axotomy (42)(43)(44), or exposure to neurotoxic substances (45). Furthermore, in some studies NGF has been reported to improve cognitive function and attenuate loss of cholinergic neurons in animal models or in patients with Alzheimer's disease (46)(47)(48).…”

Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

“…ALCAR participates in maintenance and repair processes in neurons, is able to attenuate the rate of neuronal mortality (Manfridi et al 1992) and to decrease the neurotoxicity evoked by mitochondrial uncoupling factors or inhibitors (Virmani et al 1995). ALCAR is also able to reduce the oxidative stress induced at the mitochondrial level by stimulant drug as 3,4-methylenedioximethamphetamine (Alves et al 2009).…”

Oxidative damage and mitochondrial decay in aging.

“…ALCAR's effect on mitochondrial function in the aging brain is supported by its ability to create a shift in ATP production from glycolytic pathways to mitochondria (97). In vitro studies indicate that ALCAR increases the number of N-methyl-D-aspartate (NMDA) receptors of cultured cerebellar granule cells, prevents age-associated reduction of nerve growth factor binding to PC12 cells (98), and attenuates the rate ofmortality in rat dorsal root ganglia neurons (99). In aged mice treated with ALCAR for 3 months, dopamine release is enhanced compared with untreated control animals.…”