Brain-derived neurotrophic factor prevents the loss of nigral neurons induced by excitotoxic striatal-pallidal lesions

Volpe, Bruce T.; Wildmann, Johannes; Altar, C. Anthony

doi:10.1016/s0306-4522(97)00424-7

Cited by 64 publications

(33 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vivo, supranigral infusion of BDNF and NT-4/5 led to significant increases in the cellular expression of glutamic acid decarboxylase (67 kDa) mRNA and in the size of GABAergic neurons in the rat substantia nigra (Arenas et al, 1996). Moreover, the transneuronal degeneration of nigral GABAergic neurons that occurs following excitotoxic lesioning of the striatum and pallidum was prevented by supranigral administration of BDNF (Volpe et al, 1998). These results suggest that nigral GABAergic neurons of the intact and injured adult can be activated by and are responsive to the neurotrophins, either directly or indirectly.…”

Section: Discussionmentioning

confidence: 99%

Expression of trkB andtrkC mRNAs by adult midbrain dopamine neurons: A double-label in situ hybridization study

1999

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Expression of trkB andtrkC mRNAs by adult midbrain dopamine neurons: A double-label in situ hybridization study

1999

View full text Add to dashboard Cite

“…NMDA sensitization of medium spiny neurons due to changes in the phosphorylation state alters the cortical glutamatergic input to the striatum, modifies the GABAergic output, and alters motor function (Chase and Oh, 2000). Also, striatonigral/striatopallidial GABAergic neuronal dysfunction in PD may increase or redistribute nigral iron to cause substantia nigral neuronal death (Volpe et al, 1998).…”

mentioning

confidence: 99%

5-Hydroxytryptamine 1A Receptor Activation Protects againstN-Methyl-d-aspartate-Induced Apoptotic Cell Death in Striatal and Mesencephalic Cultures

Madhavan

Freed

Anantharam

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Apoptosis and glutamate-mediated excitotoxicity may play a role in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD). In the present study, we investigated whether stimulation of the 5-hydroxytryptamine 1A (5-HT1A) receptor attenuates N-methyl-D-aspartate-(NMDA) and 1-methyl-4-phenylpyridinium (MPP ϩ )-induced apoptotic cell death in cell culture models. A brief exposure (20 min) of M213-2O striatal cells to NMDA and glutamate produced a delayed increase in caspase-3 activity and DNA fragmentation in a dose-and time-dependent manner. NMDA-induced caspase-3 activity and DNA fragmentation were almost completely blocked by the 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and (R)-5-fluoro-8 hydroxy-2-(dipropylamino)-tetralin (R-UH-301). Additionally, the protective effects of 8-OH-DPAT and R-UH-301 on NMDA-induced caspase-3 activation and apoptosis were reversed by pretreatment with the 5-HT1A antagonists N- [2-[4-(2-methoxyphenyl(WAY 100635) and S-UH-301, respectively. Similarly, doseand time-dependent increases in caspase-3 activity and DNA fragmentation were observed in rat primary mesencephalic neurons after a brief exposure to NMDA and glutamate. Caspase-3 activation and DNA fragmentation in primary mesencephalic neurons were almost completely inhibited by 8-OH-DPAT. This neuroprotective effect of 8-OH-DPAT was reversed by WAY 100635. Additionally, 8-OH-DPAT blocked tyrosine hydroxylase (TH)-positive cell death after NMDA exposure and also almost completely attenuated the NMDA-induced Ca 2ϩ influx in primary mesencephalic cultures. Furthermore, 8-OH-DPAT and R-UH-301 blocked apoptotic cell death in the primary mesencephalic neurons that were exposed to the Parkinsonian toxin MPP ϩ . Together, these results suggest that 5-HT1A receptor stimulation may be a promising pharmacological approach in the development of neuroprotective agents for PD.Parkinson's disease (PD) is a major neurodegenerative disorder with a lifetime incidence of 1 to 2%. The drug L-DOPA has been the gold standard PD treatment for more than three decades now and can bring considerable relief from the debilitating symptoms of the disease. However, its long-term use has several limitations, including severe fluctuations in effectiveness and drug-induced involuntary movements (Fahn, 1999;Carlsson, 2002). Importantly, L-DOPA simply compensates for the dopamine deficiency in Parkinson's patients and fails to attenuate the progression of the disease. Hence, novel neuroprotective agents designed to interfere with the basic pathogenic mechanism of cell death in PD are clearly needed.Excitotoxic mechanisms may contribute to the nigrostriatal degeneration in PD (Greenamyre, 1993;Olanow and Tatton, 1999). Glutamate binds to a variety of excitatory amino acid receptors, especially the NMDA receptor, leading to prolonged and excessive depolarization and neuronal activation resulting in the death of target neurons (Choi, 1988;

show abstract

“…Infusion of BDNF to the midbrain has been used in models of Parkinson's disease. The BDNF infusions reduce vestibular deficits, increase neuronal metabolism, and prevent degeneration of nigral neurons (Altar et al, 1994;Volpe et al, 1998). Intraventricular infusion of nerve growth factor (NGF) has been shown to promote the survival of cholinergic neurons, improve cognitive function, and reduce apoptosis in various rat models of traumatic brain injury (Dixon et al, 1997;Sinson et al, 1995Sinson et al, , 1997.…”

Section: Pump-catheter Systemsmentioning

confidence: 99%

Localized cell and drug delivery for auditory prostheses

et al. 2008

View full text Add to dashboard Cite

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness.

show abstract

Brain-derived neurotrophic factor prevents the loss of nigral neurons induced by excitotoxic striatal-pallidal lesions

Cited by 64 publications

References 47 publications

Expression of trkB andtrkC mRNAs by adult midbrain dopamine neurons: A double-label in situ hybridization study

Expression of trkB andtrkC mRNAs by adult midbrain dopamine neurons: A double-label in situ hybridization study

5-Hydroxytryptamine 1A Receptor Activation Protects againstN-Methyl-d-aspartate-Induced Apoptotic Cell Death in Striatal and Mesencephalic Cultures

Localized cell and drug delivery for auditory prostheses

Contact Info

Product

Resources

About