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Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
Contributor:Skup, Małgorzata (1954- ) : Supervisor
Publisher:Nencki Institute of Experimental Biology PAS
Place of publishing: Date issued/created: Description:134 pages : illustrations ; 30 cm ; Bibliography ; Summary in Polish
Degree grantor:Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
Type of object: Subject and Keywords:AMPAR ; GABAR ; GlyR ; Hyperexcitability ; Motoneurons ; NMDAR ; Spasticity ; Spinal cord injury
Abstract:Studies using spinal cord injury (SCI) models investigated molecular changes in neurotransmission-related molecules in motoneurons (MNs) mostly at the late postlesion phase, when hyperexcitability considered to be the reason of muscle spasticity is well established. However, in experimental SCI in rodents the onset of spasticity is seen as early as one week postinjury. Patterns and relations of expression level of genes coding for membrane proteins instrumental for excitatory vs inhibitory neurotransmission in the subacute phase of SCI when excitability starts to restore, are not clear.The aim of my work was to clarify the direction and extent of transcriptional regulation of receptors mediating excitatory and inhibitory neurotransmission and of functionally associated channels in hindlimb MNs of adult rats, at the second week postinjury. I hypothesized that fast molecular changes in lumbar MNs develop in response to the loss of inputs. These responses may disturb the balance of excitatory and inhibitory receptors and related ion channels in MNs. Because after SCI the extent of impairment of inputs to MNs innervating extensor and flexor muscles operating at the ankle joint is different, I examined separately MN pools innervating ankle extensor (Gastrocnemius lateralis; GL) and flexor (Tibialis anterior; TA) muscles.A promising way to treat SCI is by spinal cord enrichment with brain derived neurotrophic factor (BDNF). Previous studies showed that BDNF overexpression induced with AAV-BDNF injection caudal to the lesion site improves locomotor abilities and upregulates transcript levels of glutamatergic and GABAergic markers in the interneurons, presynaptic to MNs. While the study showed beneficial role of BDNF in adapting the network to increased activity, undesirable behavioral effects suggesting overexcitability were observed in time, which set my second aim: to characterize the effect of spinal AAV-BDNF administration on gene expression studied in the first part of my project, and identify target molecules of pro-excitogenic potential.Prior to complete spinal cord transection (SCT) at the thoracic Th11 level, retrograde tracers were injected to the respective muscles to identify MNs. After SCT, PBS or AAV-BDNF was injected bilaterally to the lumbar L1/2 segment. Non-lesioned rats with injected tracers served as controls. At two weeks postlesion, locomotor performance of spinal rats was evaluated on a running treadmill. After animal perfusion, GL and TA MNs were isolated from longitudinal spinal sections by laser-assisted microdissection, mRNA was isolated and reverse- transcribed into cDNA. Transcript levels of selected neurotransmitter receptors, ion channels and Cl- transporters were assayed using quantitative PCR.
Resource type: Detailed Resource Type: Source: Language: Language of abstract: Digitizing institution:Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Original in:Library of the Nencki Institute of Experimental Biology PAS
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