Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulate the phenotype and prevent degenerative changes in striatal projection neurons after excitotoxicity in vivo

Pérez‐Navarro, Esther; Alberch, Jordi; Neveu, Isabelle; Arenas, Ernest

doi:10.1016/s0306-4522(98)00723-4

Cited by 62 publications

(69 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While this observation must be interpreted cautiously due to the smaller number of control (n=4) versus BDNF treated cochleae (n=6), such an increase in SGN soma area associated with exogenous BDNF treatment is consistent with similar results using guinea pigs (21). Although the mechanisms underlying this increase in soma area remain unclear, studies of striatal projection neurons have also demonstrated that exogenous BDNF results in an increase in soma area when associated with neural rescue (22).…”

Section: Exogenous Application Of Bdnf In the Rat Cochlea Rescues Sgnsmentioning

confidence: 99%

Exogenous BDNF Rescues Rat Spiral Ganglion Neurons In Vivo

McGuinness¹,

Shepherd²

2005

Otology &Amp; Neurotology

106

View full text Add to dashboard Cite

The loss of hair cells resulting in a sensorineural hearing loss (SNHL) also leads to the secondary degeneration of spiral ganglion neurons (SGNs). The effectiveness of cochlear implantation in patients with a profound SNHL relies, in part, upon the survival of SGNs; therefore any therapy that can prevent or halt the loss of these neurons would be of potential clinical benefit. Previous research has shown that intracochlear infusion with neurotrophins can provide trophic support to SGNs in deafened guinea pigs. It remains to be determined whether this effect is seen in other species. After documenting the rate of SGN degeneration following ototoxic deafening, we investigated the trophic effects of exogenous brain-derived neurotrophic factor (BDNF) on rat SGNs. The left cochleae of profoundly deafened rats were implanted with a drug delivery system connected to a mini-osmotic pump. BDNF or artificial perilymph (AP) was infused for 28 days and the cochleae were then prepared for histology. Treatment with BDNF led to a statistically significant increase in SGN density and a highly significant increase in SGN soma area compared to AP-treated and untreated deafened cochleae. This work has demonstrated the trophic advantage of exogenous BDNF in the mature rat cochlea and provides confidence that SGN rescue following SNHL with exogenous BDNF may have clinical application.

show abstract

Section: Exogenous Application Of Bdnf In the Rat Cochlea Rescues Sgnsmentioning

confidence: 99%

Exogenous BDNF Rescues Rat Spiral Ganglion Neurons In Vivo

McGuinness¹,

Shepherd²

2005

Otology &Amp; Neurotology

106

View full text Add to dashboard Cite

show abstract

“…The soma area of 10 randomly chosen cells per section was outlined and the emulsion autoradiography grains were counted using the AnalySIS program (Software Imaging System GmbH) as described elsewhere (Perez-Navarro et al 1999).…”

Section: Dopamine Measurementsmentioning

confidence: 99%

“…Wt-htt increases the transcription of the brain-derived neurotrophic factor (BDNF) (Zuccato et al 2001), a neuroprotective factor for striatal (Bemelmans et al 1999;Perez-Navarro et al 1999Kells et al 2004) and dopaminergic neurons (Hyman et al 1991). This beneficial activity of wt-htt is lost when the protein is mutated as, under these conditions, BDNF expression is reduced (Ferrer et al 2000;Zuccato et al 2001Zuccato et al , 2003.…”

mentioning

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

View full text Add to dashboard Cite

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...

show abstract

“…BDNF is expressed within the hypothalamus 88 , where it is associated with satiety/appetite 89,90 , and also in the hippocampus, from where the BDNF protein is transported to the striatum and promotes survival of striatal neurons [91][92][93][94][95] . Reduced BDNF levels are associated with…”

Section: D-kefs Trail Makingmentioning

confidence: 99%