BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra

Abstract

Brain-derived neurotrophic factor (BDNF), present in minute amounts in the adult central nervous system, is a member of the nerve growth factor (NGF) family, which includes neurotrophin-3 (NT-3). NGF, BDNF and NT-3 all support survival of subpopulations of neural crest-derived sensory neurons; most sympathetic neurons are responsive to NGF, but not to BDNF; NT-3 and BDNF, but not NGF, promote survival of sensory neurons of the nodose ganglion. BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro. However, knowledge of their precise physiological role in development and maintenance of the nervous system neurons is still limited. The BDNF gene is expressed in many regions of the adult CNS, including the striatum. A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently similar to those of BDNF, can enhance the survival of dopaminergic neurons in mesencephalic cultures. BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease. Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra.

BDNF in schizophrenia, depression and corresponding animal models

“…BDNF has survival-promoting actions on a variety of CNS neurons including hippocampal and cortical neurons, 26,27 cholinergic, 28 nigral dopaminergic, 29 and 5-HT neurons. 30 Thus, within the hippocampus, neurons from the BDNF knockout mice exhibited enhanced cell death compared with cells from the wild-type animals.…”

“…27 BDNF prevents the spontaneous death of dopaminergic neurons in rat primary mesencephalic cultures 31,32 and protects TH-immunoreactive neurons from the selective toxin MPP þ (1-methyl-4-phenylpyridinium). 29 Repeated intrastriatal injections of BDNF protect from damage induced by intrastriatal administration of 6-OHDA, 33 with moderate preserving of striatal dopaminergic nerve endings around the injection site. Likewise, direct nigral infusion of BDNF protects against reductions in striatal dopamine content induced by neurotoxins in the mouse.…”

Brain‐derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) study

“…BDNF is involved in the survival and differentiation of dopaminergic neurons in the developing brain [Hyman et al, 1991], and plays an important role in the formation and the plasticity of synaptic connections [Binder & Scharfman, 2004]. BDNF is trophic for serotonergic neurons, and abnormalities in serotonin levels are the most common biochemical findings in autism [Anderson, 2002;Tsai, 2005].…”

Trophic Support of Motoneurons: Physiological, Pathophysiological, and Therapeutic Implications

“…In this context, it should be emphasized that, according to currently available information, there is not a single human or animal degenerative disease of the nervous system which can causally be linked to an insufficient or false (mutated) production of neurotrophic molecule (98). However, neurotrophic molecules have been demonstrated to rescue specific neurons from the consequences of a variety of mechanical (axotomy) or chemical (6-hydroxydopamine, MPTP, excitotoxic amino acids) damages (40,45,50,79,93,96,104,107). Therefore, the use of neurotrophic molecules in the treatment of degenerative diseases ofthe nervous system is a symptomatic one and strongly encourages further investigations aimed at a molecular understanding of the pathogenetic mechanisms of degenerative disorders of the nervous system.…”