Neurotrophin trafficking by anterograde transport

Altar, C. Anthony; DiStefano, Peter S.

doi:10.1016/s0166-2236(98)01273-9

Cited by 293 publications

(184 citation statements)

References 42 publications

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“…28 It should be mentioned, however, that BDNF is not as effective as the related and structurally similar NGF in both protection and recovery of the forebrain cholinergic neurons. 39,40 Recent findings demonstrated that BDNF is anterogradely transported in the CNS, a fact that considerably expands the concept of neuronal-derived trophic support and offers some support for the hypothesis that BDNF, in similarity to neurotransmitters, can act at the synaptic level, 41 and might thus have a broader function than assumed previously. Also, numerous central neurons coexpress BDNF and its receptor TrkB.…”

Section: Bdnf Gives Trophic Support To a Variety Of Cns Neuronsmentioning

confidence: 73%

BDNF in schizophrenia, depression and corresponding animal models

2005

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Understanding the etiology and pathogenesis schizophrenia and depression is a major challenge facing psychiatry. One hypothesis is that these disorders are secondary to a malfunction of neurotrophic factors. Inappropriate neurotrophic support during brain development could lead to structural disorganisation in which neuronal networks are established in a nonoptimal manner. Inadequate neurotrophic support in adult individuals could ultimately be an underlying mechanism leading to decreased capacity of brain to adaptive changes and increased vulnerability to neurotoxic damage. Brain-derived neurotrophic factor (BDNF) is a mediator involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system (CNS). In this review, we summarize findings regarding altered BDNF in schizophrenia and depression and animal models, as well as the effects of antipsychotic and antidepressive treatments on the expression of BDNF. Molecular Psychiatry (2005) 10, 345-352.

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Section: Bdnf Gives Trophic Support To a Variety Of Cns Neuronsmentioning

confidence: 73%

BDNF in schizophrenia, depression and corresponding animal models

2005

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“…The delayed effect on feeding inhibition suggests that BDNF in the VMH may trigger activation and/or inhibition of neural circuit(s) or may be transported to other sites for the action (1,54), for which further studies are needed. Together, these data implicate the VMH as an important site of BDNF action to influence energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

Wang

Bomberg²,

Levine³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent studies show that brainderived neurotrophic factor (BDNF) decreases feeding and body weight after peripheral and ventricular administration. BDNF mRNA and protein, and its receptor TrkB, are widely distributed in the hypothalamus and other brain regions. However, there are few reports on specific brain sites of actions for BDNF. We evaluated the effect of BDNF, given into the ventromedial nucleus of the hypothalamus (VMH), on normal and deprivation-and neuropeptide Y (NPY)-induced feeding behavior and body weight. BDNF injected unilaterally or bilaterally into the VMH of food-deprived and nondeprived rats significantly decreased feeding and body weight gain within the 0-to 24-h and the 24-to 48-h postinjection intervals. Doses effectively producing inhibition of feeding behavior did not establish a conditioned taste aversion. BDNF-induced feeding inhibition was attenuated by pretreatment of the TrkB-Fc fusion protein that blocks binding between BDNF and its receptor TrkB. VMH-injected BDNF significantly decreased VMH NPY-induced feeding at 1, 2, and 4 h after injection. In summary, BDNF in the VMH significantly decreases food intake and body weight gain, by TrkB receptor-mediated actions. Furthermore, the anorectic effects of BDNF in this site appear to be mediated by NPY. These data suggest that the VMH is an important site of action for BDNF in its effects on energy metabolism. food intake; body weight THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS (VMH) is a brain area important to the regulation of energy metabolism. Early studies indicated that VMH lesions resulted in hyperphagia and obesity (28,38,66), whereas electrical stimulation of the VMH immediately suppressed feeding and induced lipolysis (65). Glucose-sensing neurons (7,27,55,74,75) and receptors for neuropeptides important to energy metabolism have been identified in the VMH, including leptin (13,17,20,22,51), melanocortin (26), neuropeptide Y (NPY) (43), corticotrophin-releasing hormone (49), CCK (12), insulin (33), and orexin (44) receptors. Many biological agents given into the VMH have been demonstrated to affect feeding. Food intake is inhibited by administration of histamine (4, 47), glucagon-like peptide 1 (70), serotonin agonists (25), urocortin (58), CCK (79), leptin (51), and insulin (78), whereas thyroid hormone (3,5,3Ј-triiodothyronine) (40), GABA or GABA agonists (32,34,35), norepinephrine (73), orexin (74), and NPY induce feeding after administration into the VMH (5,9,24,31,43,56,76).Anatomically, the VMH receives inputs from regions important to the regulation of energy metabolism, including the hypothalamic arcuate nucleus (ARC) (2, 14, 23), lateral hypothalamus (18, 67, 80), amygdala (45, 50), and lateral septum. The VMH also projects to ARC (77), paraventricular nucleus (PVN) (42, 52), lateral hypothalamus (72, 80), dorsomedial nucleus of the hypothalamus (46, 80), amygdala (6, 68), lateral septum (68), ventral tegmental area (68), nucleus accumbens (6), and nucleus of the solitary tract (6). These behavioral and neuroanatom...

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“…Similarly, a recent report showed that mutant htt affects the vesicular transport of BDNF (Gauthier et al 2004) and therefore BDNF may be accumulated in the SN, the area in which it is produced. In fact, it has been shown that BDNF is synthesized by dopaminergic neurons of the SN (Aliaga et al 2000;Rite et al 2003;Canudas et al 2005) and transported anterogradely to the striatum by nigral afferents (Altar and DiStefano 1998). Furthermore, the inhibition of axonal transport with intracerebroventricular injections of colchicine elevates BDNF protein staining in cell bodies of cortical and nigral neurons, but depletes it within the neostriatum (Altar and DiStefano 1998).…”

Section: Discussionmentioning

confidence: 99%

Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease

Pineda¹,

Canals²,

Bosch³

et al. 2005

Journal of Neurochemistry

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Dysfunction of dopaminergic neurons may contribute to motor impairment in Huntington's disease. Here, we study the role of brain-derived neurotrophic factor (BDNF) in alterations of the nigrostriatal system associated with transgenics carrying mutant huntingtin. Using huntingtin-BDNF +/-double-mutant mice, we analyzed the effects of reducing the levels of BDNF expression in a model of Huntington's disease (R6/1). When compared with R6/1 mice, these mice exhibit an increased number of aggregates in the substantia nigra pars compacta. In addition, reduction of BDNF expression exacerbates the dopaminergic neuronal dysfunction seen in mutant huntingtin mice, such as the decrease in retrograde labelling of dopaminergic neurons and striatal dopamine content. However, mutant huntingtin mice with normal or lowered BDNF expression show the same decrease in the anterograde transport, number of dopaminergic neurons and nigral volume. In addition, reduced BDNF expression causes decreased dopamine receptor expression in mutant huntingtin mice. Examination of changes in locomotor activity induced by dopamine receptor agonists revealed that, in comparison with R6/1 mice, the double mutant mice exhibit lower activity in response to amphetamine, but not to apomorphine. In conclusion, these findings demonstrate that the decreased BDNF expression observed in Huntington's disease exacerbates dopaminergic neuronal dysfunction, which may participate in the motor disturbances associated with this neurodegenerative disorder. Keywords: amphetamine, axonal transport, movement disorders, neuronal dysfunction, neurotrophins, substantia nigra. J. Neurochem. (2005Neurochem. ( ) 93, 1057Neurochem. ( -1068 Neurodegenerative disorders are characterized by a progressive and specific loss of neurons. Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by unstable expanded CAG repeats in the 5¢-coding region of the huntingtin (htt) gene (The Huntington's Disease Collaborative Research Group 1993). The primary brain region affected in HD is the striatum, where a selective degeneration of GABAergic projection neurons occurs. However, neuronal degeneration also extends to other brain areas, including the cerebral cortex, substantia nigra (SN), globus pallidus and subthalamic nucleus as the disease progresses (Rubinsztein 2002;Browne and Beal 2004).The important role of the SN dopaminergic system in the control of motor function suggests that dysfunctional dopaminergic transmission may play a role in motor disturbances, the most common feature of HD (Hickey et al. 2002). In fact, reduced expression of dopamine receptors and Received August 6, 2004; revised manuscript received December 10, 2004; accepted December 14, 2004. Address correspondence and reprint requests to Dr J. Alberch, Departament de Biologia CelAElular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, C/Casanova, 143 E-08036 Barcelona, Spain. E-mail: alberch@ub.eduAbbreviations used: BDA, biotinylated dextran am...

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Neurotrophin trafficking by anterograde transport

Cited by 293 publications

References 42 publications

BDNF in schizophrenia, depression and corresponding animal models

BDNF in schizophrenia, depression and corresponding animal models

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

Brain‐derived neurotrophic factor modulates dopaminergic deficits in a transgenic mouse model of Huntington's disease

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