Neurotrophin-3 Rescues Striatal Synaptic Plasticity in Model of Neurodegeneration by PLC Signaling Activation.

Background: Neurotrophins are essential factors for neural growth and function; they play a crucial role in neurodegenerative diseases where their expression levels are altered. Our previous research has demonstrated changes in synaptic plasticity and neurotrophin expression levels in a pharmacological model of Huntington's disease (HD) induced by 3-nitropropionic acid (3-NP). In the 3-NP-induced HD model, corticostriatal Long Term Depression (LTD) was impaired, but neurotrophin- 3 (NT-3) restored striatal LTD.

Similarities in cognitive impairment between recent- onset and chronic schizophrenia patients: a consideration for the neurodevelopmental hypothesis.

Impairment in attention, memory, processing speed and executive functions have been described in patients with schizophrenia. Such impairments can be observed in early stages of the disease and in chronic patients; discrepancy in findings regarding the cognitive deficits at different stages of the illness keeps the debate about schizophrenia as a neurodegenerative condition which courses with continuous deterioration, or if deficits remain stable, as the neurodevelopmental hypothesis suggests.

Cognitive performance in preschoolers with non-syndromic craniosynostosis undergoing surgery: A comparison with typically developing children.

This study aimed to determine the cognitive profile of preschool children undergoing surgery to correct non-syndromic craniosynostosis, compare them with typically developing children, and analyze possible cognitive deficits in the most prevalent subtypes: sagittal and unicoronal. Thirty-one children aged 3 years to 5 years and 11 months with non-syndromic craniosynostosis (11 sagittal, 9 unicoronal, 4 metopic, 3 lambdoid, 4 multisutural) who underwent surgery were compared with thirty-one typically developing children. The Wechsler Preschool and Primary Scale of Intelligence-Third Edition (WPPSI-III) was used to assess cognitive function.

Association of α-1-Antichymotrypsin Expression with the Development of Conformational Changes of Tau Protein in Alzheimer's Disease Brain.

In Alzheimer's disease (AD), two mutually exclusive amino-terminal-dependent conformations have been reported to occur during the aggregation of Tau protein into neurofibrillary tangles (NFTs). An early conformation of full-length Tau, involving the bending of the amino terminus over the third repeated domain, is recognized by the Alz-50 antibody, followed by a second conformation recognized by Tau-66 antibody that depends on the folding of the proline-rich region over the third repeated domain in a molecule partially truncated at the amino- and carboxyl-termini. α-1-antichymotrypsin (ACT) is an acute phase serum glycoprotein that accumulates abnormally in the brain of AD patients, and since it is considered to promote the in vitro and in vivo aggregation of amyloid-β, we here seek further evidence that ACT may also contribute to the abnormal aggregation of Tau in AD.

Neurotrophin-3 modulates synaptic transmission.

Neurotrophin-3 (NT-3) belongs to a family of growth factors called neurotrophins whose actions are centered in the nervous system. NT-3 is structurally related to other neurotrophins like brain-derived neurotrophic factor. The expression of NT-3 starts with the onset of neurogenesis and continues throughout life.

The role of the TrkB-T1 receptor in the neurotrophin-4/5 antagonism of brain-derived neurotrophic factor on corticostriatal synaptic transmission.

This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins; brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation. The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially (brain-derived neurotrophic factor to neurotrophin 4/5). This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.

Do BDNF and NT-4/5 exert synergistic or occlusive effects on corticostriatal transmission in a male mouse model of Huntington's disease?

Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) are trophic factors belonging to the neurotrophin family; in addition to their trophic role, both neurotrophins play an important role in modulating corticostriatal synaptic transmission. Failures in BDNF supply and mitochondrial dysfunction are among the factors involved in the striatal degeneration that occurs in Huntington's disease (HD). While the effects of BDNF have been widely studied in striatal degeneration, the role of NT-4/5 has been less addressed.

NT-4/5 antagonizes the BDNF modulation of corticostriatal transmission: Role of the TrkB.T1 receptor.

Neurotrophins are related to survival, growth, differentiation and neurotrophic maintenance as well as modulation of synaptic transmission in different regions of the nervous system. BDNF effects have been studied in the striatum due to the trophic role of BDNF in medium spiny neurons; however, less is known about the effects of NT-4/5, which is also present in the striatum and activates the TrkB receptor along with BDNF. If both neurotrophins are present in the striatum, the following question arises: What role do they play in striatal physiology? Thus, the aim of this study was to determine the physiological effect of the sequential application and coexistence of BDNF and NT-4/5 on the modulation of corticostriatal synapses.

Striatal Neurodegeneration that Mimics Huntington's Disease Modifies GABA-induced Currents.

Huntington's Disease (HD) is a degenerative disease which produces cognitive and motor disturbances. Treatment with GABAergic agonists improves the behavior and activity of mitochondrial complexes in rodents treated with 3-nitropropionic acid to mimic HD symptomatology. Apparently, GABA receptors activity may protect striatal medium spiny neurons (MSNs) from excitotoxic damage.

Neurotrophin-3 restores synaptic plasticity in the striatum of a mouse model of Huntington's disease.

Aims: Neurotrophin-3 (NT-3) is expressed in the mouse striatum; however, it is not clear the NT-3 role in striatal physiology. The expression levels of mRNAs and immune localization of the NT-3 protein and its receptor TrkC are altered in the striatum following damage induced by an in vivo treatment with 3-nitropropionic acid (3-NP), a mitochondrial toxin used to mimic the histopathological hallmarks of Huntington's disease (HD). The aim of this study was to evaluate the role of NT-3 on corticostriatal synaptic transmission and its plasticity in both the control and damaged striatum.

Raw data of the effects of Chlorogenic acid in 3-Nitropropionic acid induced toxicity and genotoxicity.

The raw data showed in this article comes from the published research article entitled "Protective effects of Chlorogenic acid in 3-Nitropropionic acid induced toxicity and genotoxicity" Food Chem Toxicol. 2017 May 3. pii: S0278-6915(17)30226-0.

Protective effects of chlorogenic acid in 3-nitropropionic acid induced toxicity and genotoxicity.

Mitochondrial inhibition with the toxin 3-Nitropropionic acid (3-NP) has been used to study the underlying mechanisms in striatal neurodegeneration, but few experiments have evaluated its toxicity and genotoxicity of in vivo administration. Furthermore, different antioxidant molecules may prevent degeneration induced by the toxic effects of 3-NP. Therefore, the purpose of this study was to evaluate the toxicity and genotoxicity induced by 3-NP (15 mg/kg) in the micronuclei assay method; also, we assessed chlorogenic acid (CGA, 100 mg/kg) for its anti-toxic and anti-genotoxic effect in damage produced by in vivo treatment with 3-NP.

Corrigendum to "Dopaminergic Modulation of Striatal Inhibitory Transmission and Long-Term Plasticity".

[This corrects the article DOI: 10.1155/2015/789502.].

Dopaminergic Modulation of Striatal Inhibitory Transmission and Long-Term Plasticity.

Dopamine (DA) modulates glutamatergic synaptic transmission and its plasticity in the striatum; however it is not well known how DA modulates long-term plasticity of striatal GABAergic inhibitory synapses. This work focused on the analysis of both dopaminergic modulation of inhibitory synapses and the synaptic plasticity established between GABAergic afferents to medium spiny neurons (MSNs). Our results showed that low and high DA concentrations mainly reduced the amplitude of inhibitory synaptic response; however detailed analysis of the D1 and D2 participation in this modulation displayed a wide variability in synaptic response.

The Cdk5 inhibitor Roscovitine increases LTP induction in corticostriatal synapses.

In corticostriatal synapses, LTD (long-term depression) and LTP (long-term potentiation) are modulated by the activation of DA (dopamine) receptors, with LTD being the most common type of long-term plasticity induced using the standard stimulation protocols. In particular, activation of the D1 signaling pathway increases cAMP/PKA (protein kinase A) phosphorylation activity and promotes an increase in the amplitude of glutamatergic corticostriatal synapses. However, if the Cdk5 (cyclin-dependent kinase 5) phosphorylates the DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa) at Thr75, DARPP-32 becomes a strong inhibitor of PKA activity.

Circadian dysfunction in response to in vivo treatment with the mitochondrial toxin 3-nitropropionic acid.

Sleep disorders are common in neurodegenerative diseases including Huntington's disease (HD) and develop early in the disease process. Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases. In the present study, we evaluated the circadian system of mice after inhibiting mitochondrial complex II of the respiratory chain with the toxin 3-nitropropionic acid (3-NP).

Low doses of 3-nitropropionic acid in vivo induce damage in mouse skeletal muscle.

Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases and in some well-described myopathies. In the present study, we evaluated muscle changes in vivo after blocking the mitochondrial complex II of the respiratory chain by using 3-nitropropionic acid (3-NP). This neurotoxin has been used as a pharmacological tool in animal models to address some of the metabolic modifications that might underlie central neurodegeneration; however, changes in peripheral musculature have not been documented.

Dopamine reduction of GABA currents in striatal medium-sized spiny neurons is mediated principally by the D(1) receptor subtype.

Dopamine modulates voltage- and ligand-gated currents in striatal medium-sized neurons (MSNs) through the activation of D1- and D2-like family receptors. GABA(A) receptor-mediated currents are reduced by D1 receptor agonists, but the relative contribution of D(1) or D(5 )receptors in this attenuation has been elusive due to the lack of selective pharmacological agents. Here we examined GABA(A) receptor-mediated currents and the effects of D1 agonists on MSNs from wildtype and D(1) or D(5 )receptor knockout (KO) mice.

Differential induction of long term synaptic plasticity in inhibitory synapses of the hippocampus.

Long term synaptic plasticity has been more extensively studied in excitatory synapses, but it is also a property of inhibitory synapses. Many inhibitory synapses target hippocampal pyramidal neurons of the CA1 region. They originate from several interneuron classes that subdivide the surface area that they target on the pyramidal cell.

Striatal potassium channel dysfunction in Huntington's disease transgenic mice.

Huntington's disease (HD) is a neurodegenerative disorder that mainly affects the projection neurons of the striatum and cerebral cortex. Genetic mouse models of HD have shown that neurons susceptible to the mutation exhibit morphological and electrophysiological dysfunctions before and during development of the behavioral phenotype. We used HD transgenic mouse models to examine inwardly and outwardly rectifying K+ conductances, as well as expression of some related K+ channel subunits.

Similar synapse density in layer IV columns of the primary somatosensory cortex of transgenic mice with different brain size: implications for mechanisms underlying the differential allocation of cortical space.

The relative dimension of the areas constituting the cerebral cortex differs greatly in the brains of different mammalian species. The mechanisms by which such an evolutionary remodeling has occurred is not well understood. To begin exploring possible mechanisms, we took advantage of a transgenic mouse model in which the area of the primary somatosensory cortex (S1) shifts, to some extent independent from the area of the cortex as a whole, as a result of differences in the availability of insulin-like growth factor I (IGF-I).

Modulation of AMPA currents by D2 dopamine receptors in striatal medium-sized spiny neurons: are dendrites necessary?

Glutamatergic afferents from the neocortex constitute the major excitatory input to striatal medium-sized spiny neurons (MSNs). Glutamate's actions on MSNs are modulated by dopamine (DA) through D1 and D2 receptor families. Although D1 modulation of glutamate responses has been well-characterized, the contribution of postsynaptic D2 receptors to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses has not been studied extensively.

Morphological and electrophysiological characterization of abnormal cell types in pediatric cortical dysplasia.

The mechanisms responsible for seizure generation in cortical dysplasia (CD) are unknown, but morphologically abnormal cells could contribute. We examined the passive and active membrane properties of cells from pediatric CD in vitro. Normal- and abnormal-appearing cells were identified morphologically by using infrared videomicroscopy and biocytin in slices from children with mild to severe CD.