3-Nitropropionic acid modifies neurotrophin mRNA expression in the mouse striatum: 18S-rRNA is a reliable control gene for studies of the striatum

Abstract

Objective The aim of the present study was to determine the changes in the mRNA levels of neurotrophins and their receptors in the striatal tissue of mice treated with 3-nitropropionic acid (3-NP). Methods At 1 and 48 h after the last drug administration, the mRNA expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 as well as their receptors p75, TrkA, TrkB and TrkC, was evaluated using semi-quantitative (semi-Q) and real-time RT-PCR. β-actin mRNA and ribosomal 18S (18S rRNA) were tested as internal controls. Results 3-NP treatment did not affect mRNA expression of all neurotrophins and their respective receptors equally. Also, differences in neurotrophin and receptor mRNA expression were observed between semi-Q and real-time RT-PCR. Real-time RT-PCR was more accurate in evaluating the mRNA expression of the neurotrophins than semi-Q, and 18S rRNA was more reliable than β-actin as an internal control. Conclusion Neurotrophins and their receptors expression is differentially affected by neuronal damage produced by inhibition of mitochondrial respiration with 3-NP treatment in low, sub-chronic doses in vivo.

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

“…As shown in the present study, the modulatory effects of NT‐3 on corticostriatal synapses are mediated by TrkB activation; however, LTD was modulated and reestablished by the activation of TrkC. In previous studies, we documented a decrease in the NT‐3 levels in response to 3‐NP‐induced striatal degeneration . If the 3‐NP treatment reduced NT‐3 levels, HFS produced LTP; however, the exogenous addition of NT‐3 to the recording bath reestablished the LTD by activating TrkC receptors, the levels of which are known to be increased in this model of striatal degeneration …”

“…The progressive reduction in corticostriatal synaptic activity affects BDNF release and subsequently enhances cellular dysfunction and degeneration of the MSNs . Similar to patients with HD and the transgenic mouse model, BDNF levels are also reduced in the 3‐NP‐induced neurodegeneration model . The decreased BDNF levels will fail to trigger neuronal survival and neuronal protection of MSNs.…”

“…In previous studies, we documented a decrease in the NT-3 levels in response to 3-NP-induced striatal degeneration. 39 Neuronal damage, as evidenced by changes in synaptic activity and the number of dendritic spines in the MSNs, also produces a synaptic disconnection. 16 The progressive reduction in corticostriatal synaptic activity affects BDNF release and subsequently enhances cellular dysfunction and degeneration of the MSNs.…”

“…41 Similar to patients with HD and the transgenic mouse model, BDNF levels are also reduced in the 3-NP-induced neurodegeneration model. 16,39 The decreased BDNF levels will fail to trigger neuronal survival and neuronal protection of MSNs. However, if NT-3 is present in the striatum, it would stimulate TrkB and TrkC receptors and trigger signaling pathways related to neuroprotective mechanisms as well modulatory actions.…”

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

“…Using a 3‐NP model of HD to emulate early stages of the illness, we have shown that BDNF and TrkB expression is reduced in the striatum (Espíndola, Vilches‐Flores, & Hernandez‐Echeagaray, ; Mendoza et al, ); however, the striatal expression levels of NT‐4/5, unlike those of BDNF, are not altered in tissue from mice treated with 3‐NP. This is interesting because NT‐4/5 and BDNF exert their effects on synaptic transmission by stimulating TrkB, which in turn activates different signaling pathways (Amaral & Pozzo Miller, ; Gottschalk et al, ; Koponen, Lakso, & Castren, ; Poo, ; Reichardt, ).…”