Thesis etd-11202015-141247 |
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Thesis type
Tesi di laurea magistrale
Author
MAURO, DANIELE
URN
etd-11202015-141247
Thesis title
Ruolo di IGF-1 nel mediare gli effetti dell'arricchimento ambientale sulla maturazione della corteccia visiva
Department
BIOLOGIA
Course of study
BIOLOGIA APPLICATA ALLA BIOMEDICINA
Supervisors
relatore Prof.ssa Berardi, Nicoletta
Keywords
- arricchimento ambientale
- corteccia visiva
- EE
- enriched environment
- GABA
- IGF1
- inibition
- inibizione
- visual acuity
Graduation session start date
10/12/2015
Availability
Withheld
Release date
10/12/2085
Summary
The paradigm of enriched environment (EE) has been proven to be an excellent tool to investigate the role of experience and environment in the development and plasticity of the visual system. Amongst the molecular factors affected by EE, IGF-1 (Insulin-like growth factor-1) is one of the most likely candidates to mediate EE effects on visual development. Previous studies have shown that the expression of IGF-1 is significantly higher at postnatal day 18 (P18) in the primary visual cortex (V1) of enriched rats and that IGF-1 exogenous administration mimics EE effects on visual development. More recent observations have shown the existence of a much earlier peak of IGF-1 in the visual cortex of EE rats, evident around P6, which seems to be the crucial event for setting in motion the typical pattern of changes induced by EE on visual acuity development.
During my internship I tried to investigate the mechanisms by which the early rise of IGF-1 in the visual cortex is able to promote visual maturation. This issue was addressed evaluating the development of GABAergic inhibitory circuitry in the rat visual cortex following IGF-1 treatment, since the maturation of visual acuity depends on the maturation of intracortical inhibition.
We showed that IGF-1 was able to influence the expression of chlorine transporters, NKCC1 (importer) and KCC2 (exporter), in the visual cortex; in particular, IGF-1 hastens the occurrence of the developmental switch from higher to lower values of NKCC1/KCC2 ratio, which should correspond to a switch from excitatory to inhibitory GABA action.
To directly evaluate GABAergic synaptic current maturation we have used the technique of perforated whole cell-recording applied to pyramidal neurons in the visual cortex of P8 rats to estimate the reversal potential of chlorine (ECl) without disrupting the intracellular concentration of endogenous Cl. We found that in rats treated with IGF-1 there is a precocious shift of ECl towards more negative values, suggesting an accelerated maturation of inhibitory response to GABA.
We have then started to investigate the role of IGF-1 in promoting the maturation of the different sub-populations of inhibitory interneurons in V1, which are known to play different roles in visual development; the first subpopulation investigates has been the parvalbuminergic interneurons, identified with immunohistochemical methods. The results obtained indicate that IGF-1 promotes a faster molecular maturation of these interneurons, known to be crucial for critical period plasticity and visual acuity maturation.
Finally, considering that the brain receives an enormous amount of IGF-1 from peripheral blood flow, we wondered if the early peak of IGF-1 induced by EE is attributable to a systemic contribution or there is a contribution from cortical production. Previously it was observed that subcutaneous injections of IGF-1 are able to promote the accumulation of IGF-1 in the visual cortex at P6, leading to an increase in visual acuity comparable to that observed in animals enriched. To confirm the information obtained from this evidence we performed a qRTPCR in order to evaluate the expression of IGF1 in V1 in rats at P6. The results suggest that the peak of IGF-1 observed at P6 is entirely attributable to a systemic contribution.
During my internship I tried to investigate the mechanisms by which the early rise of IGF-1 in the visual cortex is able to promote visual maturation. This issue was addressed evaluating the development of GABAergic inhibitory circuitry in the rat visual cortex following IGF-1 treatment, since the maturation of visual acuity depends on the maturation of intracortical inhibition.
We showed that IGF-1 was able to influence the expression of chlorine transporters, NKCC1 (importer) and KCC2 (exporter), in the visual cortex; in particular, IGF-1 hastens the occurrence of the developmental switch from higher to lower values of NKCC1/KCC2 ratio, which should correspond to a switch from excitatory to inhibitory GABA action.
To directly evaluate GABAergic synaptic current maturation we have used the technique of perforated whole cell-recording applied to pyramidal neurons in the visual cortex of P8 rats to estimate the reversal potential of chlorine (ECl) without disrupting the intracellular concentration of endogenous Cl. We found that in rats treated with IGF-1 there is a precocious shift of ECl towards more negative values, suggesting an accelerated maturation of inhibitory response to GABA.
We have then started to investigate the role of IGF-1 in promoting the maturation of the different sub-populations of inhibitory interneurons in V1, which are known to play different roles in visual development; the first subpopulation investigates has been the parvalbuminergic interneurons, identified with immunohistochemical methods. The results obtained indicate that IGF-1 promotes a faster molecular maturation of these interneurons, known to be crucial for critical period plasticity and visual acuity maturation.
Finally, considering that the brain receives an enormous amount of IGF-1 from peripheral blood flow, we wondered if the early peak of IGF-1 induced by EE is attributable to a systemic contribution or there is a contribution from cortical production. Previously it was observed that subcutaneous injections of IGF-1 are able to promote the accumulation of IGF-1 in the visual cortex at P6, leading to an increase in visual acuity comparable to that observed in animals enriched. To confirm the information obtained from this evidence we performed a qRTPCR in order to evaluate the expression of IGF1 in V1 in rats at P6. The results suggest that the peak of IGF-1 observed at P6 is entirely attributable to a systemic contribution.
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