Neurochemical Research

, Volume 41, Issue 12, pp 3261–3271 | Cite as

Sensorimotor Intervention Recovers Noradrenaline Content in the Dentate Gyrus of Cortical Injured Rats

  • Laura E. Ramos-Languren
  • Gabriela García-Díaz
  • Angélica González-Maciel
  • Laura E. Rosas-López
  • Antonio Bueno-Nava
  • Alberto Avila-Luna
  • Hayde Ramírez-Anguiano
  • Rigoberto González-Piña
Original Paper


Nowadays, a consensus has been reached that designates the functional and structural reorganization of synapses as the primary mechanisms underlying the process of recovery from brain injury. We have reported that pontine noradrenaline (NA) is increased in animals after cortical ablation (CA). The aim of the present study was to explore the noradrenergic and morphological response after sensorimotor intervention (SMI) in rats injured in the motor cortex. We used male Wistar adult rats allocated in four conditions: sham-operated, injured by cortical ablation, sham-operated with SMI and injured by cortical ablation with SMI. Motor and somatosensory performance was evaluated prior to and 20 days after surgery. During the intervening period, a 15-session, SMI program was implemented. Subsequently, total NA analysis in the pons and dentate gyrus (DG) was performed. All groups underwent histological analysis. Our results showed that NA content in the DG was reduced in the injured group versus control, and this reduction was reverted in the injured group that underwent SMI. Moreover, injured rats showed reduction in the number of granule cells in the DG and decreased dentate granule cell layer thickness. Notably, after SMI, the loss of granule cells was reverted. Locus coeruleus showed turgid cells in the injured rats. These results suggest that SMI elicits biochemical and structural modifications in the hippocampus that could reorganize the system and lead the recovery process, modulating structural and functional plasticity.


Brain plasticity Hippocampus Pons Rehabilitation Diaschisis 



We thank Marisol Sosa-Noreña and Norma Chávez-García for their assistance with the experimental procedures.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


  1. 1.
    Ikeda S, Ohwatashi A, Harada K, Kamikawa Y, Yoshida A. (2013) Expected for acquisition movement exercise is more effective for functional recovery than simple exercise in a rat model of hemiplegia. Springer Plus. doi: 10.1186/2193-1801-2-517 Google Scholar
  2. 2.
    Inobe J-i, Kato T (2013) Effectiveness of finger-equipped electrode (FEE)-triggered electrical stimulation improving chronic stroke patients with severe hemiplegia. Brain Inj 27:114–119CrossRefPubMedGoogle Scholar
  3. 3.
    Peredeny JV, Westbrook GL. (2013) Structural plasticity in the dentate gyrus- revisiting a classic injury model. Front Neural Circuits. doi: 10.3389/fncir.2013.00017 Google Scholar
  4. 4.
    Gottlieb DI, Cowan WM (1973) Autoradiographic studies of the commissural and ipsilateral association connection of the hippocampus and detentate gyrus of the rat. I. The commissural connections. J Comp Neurol 149:393–422CrossRefPubMedGoogle Scholar
  5. 5.
    Soriano E, Frotscher M (1994) Mossy cells of the rat fascia dentata are glutamate-immunoreactive. Hippocampus 4:65–69CrossRefPubMedGoogle Scholar
  6. 6.
    Leranth C, Hajszan T. (2007) Extrinsic afferent systems to the dentate gyrus. Prog Brain Res 163:63–799CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Shamy JL, Buckmaster CA, Amaral DG, Calhoun ME, Rapp PR (2007) Reactive plasticity in the dentate gyrus following bilateral entorhinal cortex lesions in cynomolgus monkeys. J Comp Neurol 502:192–201CrossRefPubMedGoogle Scholar
  8. 8.
    Deller T, Del Turco D, Rappert A, Bechmann I (2007) Structural reorganization of the dentate gyrus following entorhinal denervation: species differences between rat and mouse. Prog Brain Res 163:501–528CrossRefPubMedGoogle Scholar
  9. 9.
    Ramos-Languren LE, Gonzalez-Pina R, Montes S, Chavez-Garcia N, Avila-Luna A, Baron-Flores V, Rios C (2016) Sensorimotor recovery from cortical injury is accompanied by changes on norepinephrine and serotonin levels in the dentate gyrus and pons. Behav Brain Res 297:297–306CrossRefPubMedGoogle Scholar
  10. 10.
    Gonzalez-Pina R, Bueno-Nava A, Montes S, Alfaro-Rodriguez A, Gonzalez-Maciel A, Reynoso-Robles R, Ayala-Guerrero F (2006) Pontine and cerebellar norepinephrine content in adult rats recovering from focal cortical injury. Neurochem Res 31:1443–1449CrossRefPubMedGoogle Scholar
  11. 11.
    Loughlin SE, Foote SL, Grzanna R (1986) Efferent projections of nucleus locus coeruleus: morphologic subpopulations have different efferent targets. Neuroscience 18:307–319CrossRefPubMedGoogle Scholar
  12. 12.
    Swanson LW, Hartman BK (1975) The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-beta-hydroxylase as a marker. J Comp Neurol 163:467–505CrossRefPubMedGoogle Scholar
  13. 13.
    Rosenzweig MR, Krech D, Bennett EL, Diamond MC (1962) Effects of environmental complexity and training on brain chemistry and anatomy: a replication and extension. J Comp Physiol Psychol 55:429–437CrossRefPubMedGoogle Scholar
  14. 14.
    Murphy GG (2015) Go out and play; your brain needs the exercise. Epilepsy Curr 15:223–224CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Scalha TB, Miyasaki E, Freire Vieira Lima NM, Borges G (2011) Correlations between motor and sensory functions in upper limb chronic hemiparetics after stroke. Arquivos De Neuro-Psiquiatria 69:624–629CrossRefPubMedGoogle Scholar
  16. 16.
    Xerri C, Zennou-Azogui Yi. (2014) Early and moderate sensory stimulation exerts a protective effect on perilesion representations of somatosensory cortex after focal ischemic damage. Plos One 9:e99767CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kaji R, Murase N (2001) Sensory function of basal ganglia. Mov Disord 16:593–594CrossRefPubMedGoogle Scholar
  18. 18.
    Abbate C, Trimarchi PD, Basile I, Mazzucchi A, Devalle G (2014) Sensory stimulation for patients with disorders of consciousness: from stimulation to rehabilitation. Frontiers in human neuroscience 8:616–616CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    National Research Council (1996) The guide for the care and use of laboratory animals. National Academy Press, CanadaGoogle Scholar
  20. 20.
    Norma Oficial Mexicana NOM-062-ZOO (1999) Especificaciones Técnicas para la producción, cuidado y uso de los animales de laboratorioGoogle Scholar
  21. 21.
    Festing MF (1994) Reduction of animal use: experimental design and quality of experiments. Lab Anim 28:212–221CrossRefPubMedGoogle Scholar
  22. 22.
    Hall D, Lindholm EP (1974) Organization of motor and somatosensory neocortex in albino rat. Brain Res 66:23–38CrossRefGoogle Scholar
  23. 23.
    Pantoni L, Bartolini L, Pracucci G, Inzitari D (1998) Interrater agreement on a simple neurological score in rats. Stroke 29:871–872CrossRefPubMedGoogle Scholar
  24. 24.
    Paxinos, Watson. (1998) The rat brain in stereotaxic coordinates. 4th ed. Elsevier Academic Press, San DiegoGoogle Scholar
  25. 25.
    Grzanna R, Molliver ME (1980) The locus coeruleus in the rat: an immunohistochemical delineation. Neuroscience 5:21–40CrossRefPubMedGoogle Scholar
  26. 26.
    Gonzalez-Pina R, Bueno-Nava A, Alfaro-Rodriguez A, Durand-Rivera JA (2008) Evaluation of the motor behavior in rats with cortical ablation. Revista De Neurologia 47:304–309PubMedGoogle Scholar
  27. 27.
    Machado S, Cunha M, Velasques B, Minc D, Teixeira S, Domingues CA, Silva JG, Bastos VH, Budde H, Cagy M, Basile L, Piedade R, Ribeiro P (2010) Sensorimotor integration: basic concepts, abnormalities related to movement disorders and sensorimotor training-induced cortical reorganization. Revista De Neurologia 51:427–436PubMedGoogle Scholar
  28. 28.
    Parnavelas JG, Lynch G, Brecha N, Cotman CW, Globus A (1974) Spine loss and regrowth in hippocampus following deafferentation. Nature 248:71–73CrossRefPubMedGoogle Scholar
  29. 29.
    Diekmann S, Ohm TG, Nitsch R (1996) Long-lasting transneuronal changes in rat dentate granule cell dendrites after entorhinal cortex lesion. A combined intracellular injection and electron microscopy study. Brain Pathol 6:205–214 (discussion 214–205)CrossRefPubMedGoogle Scholar
  30. 30.
    Cotman CW, Berchtold NC, Christie L-A (2007) Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30:464–472CrossRefPubMedGoogle Scholar
  31. 31.
    Sutoo De, Akiyama K (2003) Regulation of brain function by exercise. Neurobiol Dis 13:1–14CrossRefPubMedGoogle Scholar
  32. 32.
    Kattenstroth J-C, Kalisch T, Peters S, Tegenthoff M, Dinse HR. (2012) Long-erm sensory stimulation therapy improves hand function and restores cortical responsiveness in patients with chronic cerebral lesions. Three single case studies. Front Hum Neurosci 6:244CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Pasquier DA, Reinoso-Suarez F (1978) The topographic organization of hypothalamic and brain stem projections to the hippocampus. Brain Res Bull 3:373–389CrossRefPubMedGoogle Scholar
  34. 34.
    Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol Scand Suppl 367:1–48CrossRefPubMedGoogle Scholar
  35. 35.
    Van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270CrossRefPubMedGoogle Scholar
  36. 36.
    Tashiro A, Makino H, Gage FH (2007) Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J Neurosci 27:3252–3259CrossRefPubMedGoogle Scholar
  37. 37.
    Devauges V, Sara SJ (1991) Memory retrieval enhancement by locus coeruleus stimulation: evidence for mediation by beta-receptors. Behav Brain Res 43:93–97CrossRefPubMedGoogle Scholar
  38. 38.
    Sara SJ, Devauges V (1988) Priming stimulation of locus coeruleus facilitates memory retrieval in the rat. Brain Res 438:299–303CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Laura E. Ramos-Languren
    • 1
  • Gabriela García-Díaz
    • 1
  • Angélica González-Maciel
    • 2
  • Laura E. Rosas-López
    • 2
  • Antonio Bueno-Nava
    • 1
  • Alberto Avila-Luna
    • 1
  • Hayde Ramírez-Anguiano
    • 1
    • 3
  • Rigoberto González-Piña
    • 1
    • 3
  1. 1.Laboratorio de Neuroplasticidad-División de Neurociencias, Torre de InvestigaciónInstituto Nacional de RehabilitacionMexico CityMexico
  2. 2.Instituto Nacional de PediatríaMexico CityMexico
  3. 3.Universidad de las Américas ACMexico CityMexico

Personalised recommendations