Biomedical subjects

Nicoletta Berardi

Publications and source records attributed to Nicoletta Berardi.

13 recordsLinked to original sources

PubMed2006

Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment.

Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU-positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice. Failure to up-regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required for the environmental induction of neurogenesis.

Animals↗

PubMed2006

Structural and functional recovery from early monocular deprivation in adult rats.

Visual deficits caused by abnormal visual experience during development are hard to recover in adult animals. Removal of chondroitin sulfate proteoglycans from the mature extracellular matrix with chondroitinase ABC promotes plasticity in the adult visual cortex. We tested whether chondroitinase ABC treatment of adult rats facilitates anatomical, functional, and behavioral recovery from the effects of a period of monocular deprivation initiated during the critical period for monocular deprivation. We found that chondroitinase ABC treatment coupled with reverse lid-suturing causes a complete recovery of ocular dominance, visual acuity, and dendritic spine density in adult rats. Thus, manipulations of the extracellular matrix can be used to promote functional recovery in the adult cortex.

Aging↗

PubMed2005

Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice.

Nerve growth factor (NGF) delivery to the brain of patients appears to be an emerging potential therapeutic approach to neurodegenerative disease, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracere-broventricular infusion and gene therapy. We previously showed that intranasal administration of NGF determined an amelioration of cholinergic deficit and a decrease in the number of phosphotau-positive neurons and of beta-amyloid accumulation in AD11 mice, which express transgenic antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like neurodegeneration. In this study, we report that the Alzheimer-like neurodegeneration in AD11 mice is linked to progressive behavioral deficits in visual recognition memory and spatial memory starting from 4 months of age. To establish whether intranasal administration of NGF, started after the appearance of the first memory deficits, could revert the cognitive deficits in AD11 mice, we assessed the performance of NGF-treated or control AD11 mice in the object recognition test and in a test of memory for place and context. Deficits exhibited by untreated AD11 mice could be rescued by the intranasal administration of NGF. Thus, this route of administration provides a promising way to deliver NGF to the brain in a therapeutic perspective.

Administration, Intranasal↗

PubMed2004

Extracellular matrix and visual cortical plasticity: freeing the synapse.

The effects of monocular deprivation (MD) on the ocular dominance of visual cortical neurons are a paradigmatic example of experience-dependent plasticity. Here we review recent data showing that extracellular matrix (ECM) plays an important role in the control of experience-dependent plasticity both in the developing and adult visual cortex.

Animals↗

PubMed2004

Acceleration of visual system development by environmental enrichment.

Thus far, the developmental plasticity of the visual system has been studied by altering or reducing visual experience. Here, we investigated whether a complex sensory-motor stimulation, provided by rearing animals in an enriched environment, affects visual system development. We found that raising mice in this condition causes an earlier eye opening, a precocious development of visual acuity, and an accelerated decline of white matter-induced long-term potentiation. These effects are accompanied by a precocious cAMP response element-mediated gene expression and a significant increase of BDNF protein and GAD65/67 expression in enriched pups. In addition, we showed that enriched pups experienced higher levels of licking behavior provided by adult females. Thus, rearing mice from birth in an enriched environment leads to a conspicuous acceleration of visual system development as ascertained at behavioral, electrophysiological, and molecular level.

Animals↗

PubMed2004

Environmental enrichment prevents effects of dark-rearing in the rat visual cortex.

Environmental enrichment potentiates neural plasticity, enhancing acquisition and consolidation of memory traces. In the sensory cortices, after cortical circuit maturation and sensory function acquisition are completed, neural plasticity declines and the critical period 'closes'. In the visual cortex, this process can be prevented by dark-rearing, and here we show that environmental enrichment can promote physiological maturation and consolidation of visual cortical connections in dark-reared rats, leading to critical period closure.

Animals↗

PubMed2004

Enriched environment and acceleration of visual system development.

Rearing mice from birth in an enriched environment leads to a conspicuous acceleration of visual system development appreciable at behavioral, electrophysiological and molecular level. Little is known about the possible mechanisms of action through which enriched environment affects visual system development. It has been suggested that differences in maternal behavior between enriched and non-enriched conditions could contribute to the earliest effects of enriched environment on visual development and that neurotrophins, BDNF in particular, might be involved. Here, we examined Brain Derived Neurotrophic Factor (BDNF) levels in the visual cortex during development and showed that an increase occurs in the first week of life in enriched pups compared to standard reared pups; BDNF levels at birth were equal in the two groups. This suggests a postnatal rather than a prenatal effect of environment on BDNF. A detailed analysis of maternal care behavior showed that pups raised in a condition of social and physical enrichment experienced higher levels of licking behavior and physical contact compared to standard reared pups and that enhanced levels of licking were also provided to pups in an enriched environment where no adult females other than the mother were present. Thus, different levels of maternal care in different environmental conditions could act as indirect mediator for the earliest effects of enrichment on visual system development. Some of the effects of different levels of maternal care on the offspring behavior are long lasting. We measured the visual acuity of differentially reared mice at the end of the period of visual acuity development (postnatal day 45) and at 12 months of age, using a behavioral discrimination task. We found better learning abilities and higher visual acuity in enriched compared to standard reared mice at both ages.

Aging↗

PubMed2003

Effects of neurotrophins on synaptic protein expression in the visual cortex of dark-reared rats.

Total lack of visual experience [dark rearing (DR)] is known to prolong the critical period and delay development of sensory functions in mammalian visual cortex. Recent results show that neurotrophins (NTs) counteract the effects of DR on functional properties of visual cortical cells and exert a strong control on critical period duration. NTs are known to modulate the development and synaptic efficacy of neurotransmitter systems that are affected by DR. However, it is still unknown whether the actions of NTs in dark-reared animals involve interaction with neurotransmitter systems. We have studied the effects of DR on the expression of key molecules in the glutamatergic and GABAergic systems in control and NT-treated animals. We have found that DR reduced the expression of the NMDA receptor 2A subunit and its associated protein PSD-95 (postsynaptic density-95), of GRIP (AMPA glutamate receptor interacting protein), and of the biosynthetic enzyme GAD (glutamic acid decarboxylase). Returning dark-reared animals to light for 2 hr restored normal expression of the above-mentioned proteins almost completely. NT treatment specifically counteracts DR effects; NGF acts primarily on the NMDA system, whereas BDNF acts primarily on the GABAergic system. Finally, the action of NT4 seems to involve both excitatory and inhibitory systems. These data demonstrate that different NTs counteract DR effects by modulating the expression of key molecules of the excitatory and inhibitory neurotransmitter systems.

Animals↗

PubMed2003

Molecular basis of plasticity in the visual cortex.

Sensory experience is known to shape the maturation of cortical circuits during development. A paradigmatic example is the effect of monocular deprivation on ocular dominance of visual cortical neurons. Although visual cortical plasticity has been widely studied since its initial discovery by Hubel and Wiesel >40 years ago, the description of the underlying molecular mechanisms has lagged behind. Several new findings are now beginning to close this gap. Recent data deepen our knowledge of the factors involved in the intercellular communication and intracellular signaling that mediate experience-dependent plasticity in the developing visual cortex. In addition, new findings suggest a role for the extracellular matrix in inhibition of ocular-dominance plasticity in the adult visual cortex.

Animals↗

PubMed2003

Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions.

Neurotrophins strongly affect visual system development and plasticity. However, the mode of delivery and targets of neurotrophin action are still under debate. For instance, cortical NT-4/5 (neurotrophin 4/5; Ntf4/5) was shown to rescue lateral geniculate nucleus (LGN) neurons from monocular deprivation-induced atrophy suggesting a retrograde action on thalamic afferents. It is still unclear whether LGN neurons respond to NT-4/5 and other neurotrophins during development in animals with normal vision. We now show that infusions of NT-4/5 and NGF (nerve growth factor) into visual cortex at the onset and the peak of the critical period accelerated LGN neuron growth. BDNF (brain-derived neurotrophic factor) was ineffective. The effects of neurotrophin on LGN development were clearly dissociated from the effects at cortical level because soma growth of cortical layer IV and VI neurons was strongly promoted by BDNF. NT-4/5 was only effective at the onset, but no longer at the peak of the critical period suggesting a switch in neurotrophin dependency for these cortical cell classes. To dissociate retrograde and anterograde effects of the TrkB ligands, we analyzed the stratum griseum superficiale (SGS) of the superior colliculus, a target of visual cortical efferents. Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth. Strikingly, the TrkB-expressing excitatory tectothalamic calbindin neurons in the SGS did not respond. This demonstrated for the first time a selective cell type-specific anterograde action of NT-4/5 and suggested for the LGN that anterograde as well as retrograde effects contribute to soma size regulation. Strikingly, cortical infusion of the cytokine LIF, which affects development of visual cortex neurochemical architecture, transiently inhibited growth of neurons in LGN, cortical layer IV and VI and SGS. In summary, the study presents three important results. First, central neurons regulate soma size development in an age-and ligand-specific fashion. Second, NT-4/5 and NGF accelerate LGN development in rats with normal vision while LIF delays growth. Third, anterogradely transported NT-4/5 effectively promotes neuronal maturation. These differential actions on subcortical neurons may contribute to the different effects of neurotrophins on visual system development and plasticity.

Afferent Pathways↗

PubMed2002

Reactivation of ocular dominance plasticity in the adult visual cortex.

In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.

Animals↗

PubMed2002

Protein synthesis in the visual cortex is needed for ocular dominance plasticity.

Experience-dependent remodelling of neural connections progresses through stages, and early phases eventually give way to later long-lasting ones. The transition from early to late stages, often associated with structural changes, depends on protein synthesis. Suppression of cortical but not geniculate protein synthesis blocks ocular dominance plasticity at its earliest stage, suggesting that structural changes occur rapidly in the visual cortex following monocular deprivation.

Animals↗

PubMed2002

Effects of dark rearing on phosphorylation of neurotrophin Trk receptors.

Total lack of visual experience (dark rearing, DR) is known to affect development of mammalian visual cortex (VC) and to prolong the critical period of visual cortical plasticity. Neurotrophins (NTs) have been proposed to play a relevant role in activity dependent processes important for the final shaping of cortical visual connections. Neurotrophin supply or antagonism of endogenous NT action profoundly affect visual cortical development and plasticity; in particular, exogenous supply of NTs counteracts DR effects on VC development. However, the effects of DR on NT expression are still debated and mounting evidence reports a mismatch between BDNF mRNA and protein expression in DR animals. To gain insight into the effects of DR on expression of nerve growth factor (NGF) and the functional state of NT signalling pathways, we assessed the phosphorylation state of Trk receptors in light-reared animals (LR), in dark-reared animals (DR), in DR animals briefly exposed to light and in DR animals with exogenous supply of NTs [NGF, brain-derived neurotrophic factor (BDNF) and NT-4] in the VC. We report that DR increases the expression of NGF but reduces the phosphorylation of TrkA and TrkB receptors with respect to LR; normal phosphorylation is rapidly rescued by a brief exposure to light. Exogenous supply of NGF, BDNF or NT4 in DR animals also rescues the phosphorylation of their receptors.

Animals↗