Neuronal and brain morphological changes in animal models of schizophrenia

doi:10.1016/j.bbr.2015.12.034

Behavioural Brain Research

Volume 301, 15 March 2016, Pages 190-203

https://doi.org/10.1016/j.bbr.2015.12.034 Get rights and content

Highlights

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Schizophrenia produces neural remodeling in the prefrontal cortex in humans.
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Changes in the shape of dendritic arbor result of either gain or loss of connectivity.
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Animal models are useful tools to understand schizophrenia.
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Schizophrenia animal models present dendritic and spine density alterations.

Abstract

Schizophrenia, a severe and debilitating disorder with a high social burden, affects 1% of the adult world population. Available therapies are unable to treat all the symptoms, and result in strong side effects. For this reason, numerous animal models have been generated to elucidate the pathophysiology of this disorder. All these models present neuronal remodeling and abnormalities in spine stability. It is well known that the complexity in dendritic arborization determines the number of receptive synaptic contacts. Also the loss of dendritic spines and arbor stability are strongly associated with schizophrenia. This review evaluates changes in spine density and dendritic arborization in animal models of schizophrenia. By understanding these changes, pharmacological treatments can be designed to target specific neural systems to attenuate neuronal remodeling and associated behavioral deficits.

Graphical abstract

Section snippets

Schizophrenia

Schizophrenia is a devastating disorder not only for the patient but also for the family. Indeed, this disorder alters the relation between the patient and the family and could induce a family breakdown modifying the prognostic of the schizophrenic patient. This complex disorder affects 1% of the world’s population. Interestingly, this mental disorder starts in early adulthood during the time when synapses are pruned [1], [2] with a particular combination of positive, negative, affective

Neuronal staining as a tool to evaluate neuronal morphology

The so-called Golgi–Cox method is a histological technique widely used as a tool to study neurons in the central nervous system (CNS). This staining procedure together with the Sholl analysis for light microscopy provides information about morphology, distribution, location, and intrinsic connections of neurons. Although this method does not reveal details of the internal structure of nerve cells, it does provide a unique view of the entire neurons and the relation of dendrites and axons to the

Relevance of neuronal morphology in schizophrenia

Neuronal rearrangement and alterations in dendritic spines are observed in postmortem brains of patients with schizophrenia and numerous animal models of schizophrenia-like behavior [4] however, their causes have yet to be established [6], [7], [8]. For example, a reduced dendritic spine number has been reported in the layer 3 of the PFC in schizophrenia [9], [10], [11], [12] and this region is a major site for cortico-cortico and thalamo-cortico integration [4].

The shape of dendritic arbor of

Neurotransmitter hypothesis of the disease

Several reports suggest that the etiology of schizophrenia may be related to dopamine (DA) overactivity in the mesolimbic system [22]. Indeed, chronic administration of d-amphetamine, an indirect DA-agonist, produces schizophrenia-like behaviors in normal human beings [22]. In schizophrenic patients, administration of DA agonists exacerbates the symptoms of schizophrenia. On the contrary, antipsychotic drugs such as haloperidol, a DA D2 receptor (DAD2R) antagonist is effective in ameliorating

Cerebral key regions involved in schizophrenia

Numerous studies have documented the presence of structural changes in schizophrenic patients’ brain, including loss of cortical volume (white and gray matter), ventricular dilatation, myelinated fibers damage and glial cell abnormalities. Altogether structural and neuronal alterations provoke a damaged communication among different brain regions [28].

The volumetric changes are detected principally in prefrontal cortical areas, hippocampus and amygdala, engaged in disrupted cognitive functions

Animal models of schizophrenia-like behavior

Animal models are critical in research to further understand the disease mechanisms and design new treatments [75]. Animal models are valuable preclinical tools which investigates the neurobiological basis of schizophrenia. They offer a platform to quickly monitor numerous elements of the disease progression. Furthermore, they give the opportunity to analyze structural and molecular changes that occur in response to therapeutic agents [76].

Recently, it has been estimated, that more than twenty

Pharmacological treatment reshaping the neurons in animal models of schizophrenia

The rat model of nVHL has proven a highly valuable tool for the analysis of numerous behavioral deficits and alterations in the central nervous system including neuronal hypotrophy in several brain regions. Pioneer work from our group recently showed that Clozapine reshape neurons in animals with nVHL [109]. Indeed, Clozapine increased the TDL in neurons from the PFC, NAcc and BLA. In addition to the neuronal remodeling, this treatment dramatically decreased the hyperlocomotion in novel

Concluding remarks

Schizophrenia symptoms appear in early adulthood during the time when synapses are pruned [2]. While all animal models of schizophrenia present behavioral deficits and neuronal remodeling, studies presenting data from prepubertal animals is scarce. Thus, the search for neuronal remodeling in animal models at prepubertal age is certainly warranted to know the degree of validity of the model.

As reviewed above, animal models of schizophrenia have different origins and target various

Acknowledgements

Funding for this study was provided by project 129303 from CONACYT, Mexico (GF). CONACyT has no role in the writing or discussion of the present review. G.F., J.C.M.M. and A.D.D.F. acknowledge the National Research System (CONACYT) for membership. We thank Mira Thakur for editing and proofreading the manuscript.

References (198)

J.R. Glausier et al.
Dendritic spine pathology in schizophrenia
Neuroscience
(2013)
T.D. Cannon et al.
Decreased neurotrophic response to birth hypoxia in the etiology of schizophrenia
Biol. Psychiatry
(2008)
S. Oray et al.
Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation
Neuron
(2004)
J.C. Fiala et al.
Dendritic spine pathology: cause or consequence of neurological disorders?
Brain Res. Rev.
(2002)
S. Kapur et al.
Half a century of antipsychotics and still a central role for dopamine D2 receptors
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2003)
A.F. Arnsten et al.
Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses
Neuron
(2012)
K. Broadbelt et al.
Evidence for a decrease in basilar dendrites of pyramidal cells in schizophrenic medial prefrontal cortex
Schizophr. Res
(2002)
A.A. Grace
Gating of information flow within the limbic system and the pathophysiology of schizophrenia
Brain Res. Brain Res. Rev.
(2000)
C.A. Ross et al.
Neurobiology of schizophrenia
Neuron
(2006)
C.A. Heidbreder et al.
The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics
Neurosci. Biobehav. Rev.
(2003)

P.J. Morgane et al.

The limbic brain: continuing resolution

Neurosci. Beha. Rev.

(2006)

R.P. Kesner et al.

An analysis of rat prefrontal cortex in mediating executive function

Neurobiol. Learn. Mem.

(2011)

J.M. Fuster

The prefrontal cortex—an update: time is off essence

Neuron

(2001)

Y. Goto et al.

Prefrontal lesions reverses abnormales mesoaccumbens response in an animal model of schizophrenia

Biol. Psychiatry

(2004)

K. Dedovic et al.

The brain and the stress axis: the neural correlates of cortisol regulation in response to stress

Neuroimage

(2009)

M.S. Fanselow et al.

Are the dorsal and ventral hippocampus functionally distinct structures??

Neuron

(2010)

N. McNaughton et al.

Anxiolytic action on the behavioural inhibition system implies multiple types of arousal contribute to anxiety

J. Affect. Disord.

(2000)

J.C. Morales-Medina et al.

Morphological reorganization after repeated corticosterone administration in the hippocampus, nucleus accumbens and amygdala in the rat

J. Chem. Neuroanat.

(2009)

J.I. Tracy et al.

Anticholinergicity and cognitive processing in choronic schizophrenia

Biol. Physichol.

(2001)

A. Anticevic et al.

A broken filter: prefrontal functional connectivity abnormalities in schizophrenia during workingmemory interference

Schizophr Res.

(2012)

Y. Miyamoto et al.

J. Pharmacol. Sci.

(2014)

B. Pyndt Jørgensen et al.

Investigating the long-term effect of subchronic phencyclidine-treatment on novel object recognition and the association between the gut microbiota and behavior in the animal model of schizophrenia

Physiol. Behav.

(2015)

R.E. Featherstone et al.

The amphetamine-induced sensitized state as a model of schizophrenia

Prog. Neuropsychopharmacol. Biol. Psychiatry

(2007)

R.M. Murray et al.

Schizophrenia from developmental deviance to dopamine dysregulation

Eur. Neuropsychopharmacol.

(2008)

B.K. Lipska et al.

To model a psychiatric disorder in animals: schizophrenia as a reality test

Neuropsychopharmacology

(2000)

E.W. Daenen et al.

Neonatal lesions in the amygdala or ventral hippocampus disrupt prepulse inhibition of the acoustic startle response; implications for an animal model of neurodevelopmental disorders like schizophrenia

Eur. Neuropsychopharmacol.

(2003)

J.H. Cabungcal et al.

Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia

Neuron

(2014)

H.A. Al-Amin et al.

Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus

Biol. Psychiatry

(2001)

G. Le Pen et al.

Prepulse inhibition deficits of the startle reflex in neonatal ventral hippocampal-lesioned rats: reversal by glycine and a glycine transporter inhibitor

Biol. Psychiatry

(2003)

G. Le Pen et al.

Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by haloperidol

Neuropsychopharmacology

(2002)

A.B. Silva-Gomez et al.

Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats

Brain Res.

(2003)

G. Flores et al.

The potential of cerebrolysin in the treatment of Schizophrenia

Pharmacol. Pharm.

(2014)

A. Schmitt et al.

The impact of environmental factors in severe psychiatric disorders

Front. Neurosci.

(2014)

A. Hernandez et al.

Altered basolateral amygdala encoding in an animal model of schizophrenia

J. Neurosci.

(2015)

R.A. Sweet et al.

Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia

Front. Hum. Neurosci.

(2010)

G. Flores et al.

Characterization of Cytoarchitecture of dendrites and fiber neurons using the golgi-cox method: an overview. Chapter 8

Int. Horiz. Neurosci. Res.

(2015)

M.C. Kiernan et al.

Conduction block in carpal tunnel syndrome

Brain

(1999)

T.D. Cannon et al.

Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls

Arch. Gen. Psychiatry

(2002)

L.J. Garey et al.

Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia

J. Neurol Neurosurg. Psychiatry

(1998)

L.A. Glantz et al.

Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia

Arch. Gen. Psychiatry

(2000)

N. Kolluri et al.

Lamina-specific reductions in dendritic spine density in the prefrontal cortex of subjects with schizophrenia

Am. J. Psychiatry

(2005)

A.J. Koleske

Molecular mechanisms of dendrite stability

Nat. Rev. Neurosci.

(2013)

A. Holtmaat et al.

Experience-dependent and cell-type-specific spine growth in the neocortex

Nature

(2006)

A. Gomez-Palacio-Schjetnanm et al.

Neurotrophins and synaptic plasticity

Curr. Top. Behav. Neurosci.

(2013)

M.J. Green et al.

Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis

Mol. Psychiatry

(2011)

J. Rao et al.

Is schizophrenia a neurodegenerative disease? Evidence from age-related decline of brain-derived neurotrophic factor in the brains of schizophrenia patients and matched nonpsychiatric controls

Neurodegener. Dis.

(2015)

I. Nikonenko et al.

Nitric oxide mediates local activity-dependent excitatory synapse development

PNAS

(2013)

C. Manitt et al.

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients

Trans. Psychiatry

(2013)

O. Howes et al.

Glutamate and dopamine in schizophrenia: An update for the 21st century

J. Psychopharmacol.

(2015)

S. Geisler et al.

Functional implications of glutamatergic projections to the ventral tegmental area

Rev. Neurosci.

(2008)

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ReviewNeuronal and brain morphological changes in animal models of schizophrenia

Highlights

Abstract

Graphical abstract

Section snippets

Schizophrenia

Neuronal staining as a tool to evaluate neuronal morphology

Relevance of neuronal morphology in schizophrenia

Neurotransmitter hypothesis of the disease

Cerebral key regions involved in schizophrenia

Animal models of schizophrenia-like behavior

Pharmacological treatment reshaping the neurons in animal models of schizophrenia

Concluding remarks

Acknowledgements

Neuroscience

Biol. Psychiatry

Neuron

Brain Res. Rev.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Neuron

Schizophr. Res

Brain Res. Brain Res. Rev.

Neuron

Neurosci. Biobehav. Rev.

Neurosci. Beha. Rev.

Neurobiol. Learn. Mem.

Neuron

Biol. Psychiatry

Neuroimage

Neuron

J. Affect. Disord.

J. Chem. Neuroanat.

Biol. Physichol.

Schizophr Res.

J. Pharmacol. Sci.

Physiol. Behav.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Eur. Neuropsychopharmacol.

Neuropsychopharmacology

Eur. Neuropsychopharmacol.

Neuron

Biol. Psychiatry

Biol. Psychiatry

Neuropsychopharmacology

Brain Res.

The potential of cerebrolysin in the treatment of Schizophrenia

Pharmacol. Pharm.

The impact of environmental factors in severe psychiatric disorders

Front. Neurosci.

Altered basolateral amygdala encoding in an animal model of schizophrenia

J. Neurosci.

Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia

Front. Hum. Neurosci.

Characterization of Cytoarchitecture of dendrites and fiber neurons using the golgi-cox method: an overview. Chapter 8

Int. Horiz. Neurosci. Res.

Conduction block in carpal tunnel syndrome

Brain

Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls

Arch. Gen. Psychiatry

Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia

J. Neurol Neurosurg. Psychiatry

Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia

Arch. Gen. Psychiatry

Lamina-specific reductions in dendritic spine density in the prefrontal cortex of subjects with schizophrenia

Am. J. Psychiatry

Molecular mechanisms of dendrite stability

Nat. Rev. Neurosci.

Experience-dependent and cell-type-specific spine growth in the neocortex

Nature

Neurotrophins and synaptic plasticity

Curr. Top. Behav. Neurosci.

Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis

Mol. Psychiatry

Is schizophrenia a neurodegenerative disease? Evidence from age-related decline of brain-derived neurotrophic factor in the brains of schizophrenia patients and matched nonpsychiatric controls

Neurodegener. Dis.

Nitric oxide mediates local activity-dependent excitatory synapse development

PNAS

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients

Trans. Psychiatry

Glutamate and dopamine in schizophrenia: An update for the 21st century

Review
Neuronal and brain morphological changes in animal models of schizophrenia