Chapter title |
Taurine Recovery of Learning Deficits Induced by Developmental Pb2+ Exposure
|
---|---|
Chapter number | 4 |
Book title |
Taurine 10
|
Published in |
Advances in experimental medicine and biology, January 2017
|
DOI | 10.1007/978-94-024-1079-2_4 |
Pubmed ID | |
Book ISBNs |
978-9-40-241077-8, 978-9-40-241079-2
|
Authors |
Lorenz S. Neuwirth, Nicholas P. Volpe, Chuyon Corwin, Simon Ng, Navita Madan, Alyssa M. Ferraro, Yevgeniy Furman, Abdeslem El Idrissi |
Abstract |
Lead (Pb(2+)) is a historically well-documented environmental neurotoxin that produces developmental cognitive learning and memory impairments. These early neurodevelopmental impairments cause increased brain excitability via disruption of Ca(2+) mediated signaling during critical periods of synaptogenesis inducing competition with Ica(2+) through NMDARs resulting in altered brain development and functioning across the lifespan. Interestingly, Pb(2+) has been shown to decrease GABA transport and uptake, decrease spontaneous and depolarization-evoked GABA neurotransmission and lower the expression of glutamic acid decarboxylase (GAD); thereby, limiting excitatory GABAergic influences that regulate early developmental brain excitability and reducing inhibition across mature GABAergic networks. Taurine has been shown to regulate brain excitability in the mature brain through GABAAR mediated inhibition, thereby attenuating improper brain excitability. Mechanistically, taurine is developmentally a potent neuromodulator that acts as a GABAAR agonist and more recently has been reported as a partial agonist for NMDARs through glycine sites. We investigated the effects of developmental Pb(2+) exposure on the rat's mature inhibitory cognitive control abilities pharmacologically through anxiety and emotional learning-related behaviors and whether taurine could recover Pb(2+) induced neurodevelopmental behavioral deficits later in life. Results showed that Pb(2+) increased anxiety symptoms in the open field and hole board test, increased sensitivity to context fear training with cognitive deficits in both acquisition and extinction learning while producing learning deficits and inabilities in acquiring inhibitory learned associations through the acoustic startle response and pre-pulse inhibition (ASR-PPI) test. Interestingly, taurine recovered Pb(2+) developmentally induced behavioral deficits in the open field and hole board test evidenced by decreased freezing and increased exploration behaviors and facilitated inhibitory dependent ASR-PPI learning to levels higher than controls. In contrast, Baclofen, a GABABR agonist, dose dependently showed no interaction with Pb(2+) effects on ASR-PPI learning. Thus, taurine may work as an important neuromodulator at both GABAARs and NMDARs glycine sites, thereby increasing inhibition, enhancing Ca(2+)-mediated signaling, and decreasing the altered brain excitability, which impedes learning and memory from early Pb(2+) exposure. Taken together our data suggests that GABAAR dependent inhibitory learning is altered by early Pb(2+) exposure and taurine was able to recover these Pb(2+) induced deficits through neuromodulation of GABAARs and potentially NMDARs later in life. These findings may pave the way for further exploration of taurine as a pharmacotherapy for neurodevelopmental lead poisoning in both animal and clinical models. |
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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 22% |
Student > Bachelor | 3 | 11% |
Student > Master | 3 | 11% |
Researcher | 3 | 11% |
Student > Doctoral Student | 2 | 7% |
Other | 3 | 11% |
Unknown | 7 | 26% |
Readers by discipline | Count | As % |
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Psychology | 6 | 22% |
Neuroscience | 4 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
Medicine and Dentistry | 2 | 7% |
Agricultural and Biological Sciences | 1 | 4% |
Other | 2 | 7% |
Unknown | 10 | 37% |